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1.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 75-82, 2024.
Article in Chinese | WPRIM | ID: wpr-1006557

ABSTRACT

ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 (AMPK/PGC-1α/SIRT3) signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling, they were randomly divided into high, medium, and low dose Tangbikang granule groups (2.5, 1.25, 0.625 g·kg-1·d-1) and lipoic acid group (0.026 8 g·kg-1·d-1), and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4, 8, 12 weeks after intervention. At the 12th week, motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), nerve blood flow velocity, mechanical pain threshold, and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin (HE) staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in sciatic nerve were determined by enzyme-related immunosorbent assay (ELISA). The mRNA expressions of AMPKα, AMPKβ, PGC-1α, and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction (Real-time PCR). ResultCompared with the normal group, fasting blood glucose in the model group was increased at each time point (P<0.01). The mechanical pain threshold was decreased (P<0.05), and the incubation time of the hot plate was extended (P<0.01). MNCV, SNCV, and nerve blood flow velocity decreased (P<0.05). The expression level of SOD was decreased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were increased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were decreased (P<0.01). The structure of sciatic nerve fibers in the model group was loose, and the arrangement was disordered. The demyelination change was obvious. Compared with the model group, the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks (P<0.01). The mechanical pain threshold increased (P<0.05). The incubation time of the hot plate was shortened (P<0.01). MNCV, SNCV, and Flux increased (P<0.05). The expression level of SOD was increased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were decreased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were increased (P<0.01). The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged, with only a few demyelinating changes. The high, medium, and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

2.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 57-64, 2024.
Article in Chinese | WPRIM | ID: wpr-1006268

ABSTRACT

ObjectiveTo observe the effects of the South African herb Hoodia gordonii (HG) on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt)/factor forkhead protein O1 (FoxO1) signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose: model group, metformin group (0.195 g·kg-1), and low dose (0.39 g·kg-1), medium dose (0.78 g·kg-1), and high dose (1.56 g·kg-1) HG groups, with six m/m mice in each group, and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg-1 by gavage. Body weight, water intake, and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration, serum insulin (FINS), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine (CREA) were measured, and liver sections were embedded and stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and oil red O. Protein expression of PI3K p85, p-Akt, and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K, Akt, and FoxO1 in liver tissue was detected by real-time polymerase chain reaction (Real-time PCR). ResultAfter six weeks of administration intervention, it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups (P<0.05). The level of islet resistance index was significantly reduced in both the low and medium dose HG groups (P<0.05). The expression levels of TC, TG, and LDL were reduced in all HG groups (P<0.05, P<0.01). Pathologically, HG could alleviate hepatocyte steatosis, reduce the volume and content of lipid droplets in liver, and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low, medium, and high dose HG groups compared with the model group (P<0.01). p-Akt protein expression was significantly increased in the medium and high dose HG groups (P<0.05, P<0.01). p-FoxO1 protein expression was significantly increased in the low, medium, and high dose HG groups (P<0.05, P<0.01). Compared with the model group, PI3K mRNA was increased in low dose, medium dose, and high dose HG groups (P<0.05), and Akt mRNA was increased in high dose HG group (P<0.05). FoxO1 mRNA was decreased in low dose, medium dose, and high dose HG groups (P<0.05). ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice, which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.

3.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 247-255, 2024.
Article in Chinese | WPRIM | ID: wpr-1011465

ABSTRACT

Insulin resistance (IR) is an important pathological and physiological mechanism of type 2 diabetes (T2DM), and the treatment of IR has become the key to the prevention and treatment of T2DM. IR is a state of insensitivity or reduced sensitivity of insulin-stimulated tissue cells to glucose, resulting in cells that are unable to efficiently take up glucose in the bloodstream and thus causing hyperglycemia. Adenosine monophosphate-activated protein kinase (AMPK) is an energy-sensing enzyme that can regulate multiple metabolic pathways and maintain the stability of adenosine triphosphate (ATP) in the cell. In recent years, traditional Chinese medicine (TCM) has played an increasingly important role in the prevention and treatment of T2DM. The research on exploring the AMPK signaling pathway of TCM intervention in the progress of T2DM has gradually increased. Many pharmacological studies have shown that TCM has advantages such as safety and high efficiency in the prevention and treatment of T2DM. AMPK signaling pathway is one of the key pathways for the active ingredients of TCM and TCM extracts to improve IR. Active ingredients such as phenols, flavonoids, polysaccharides, alkaloids, and saponins, as well as other herbal extracts can improve IR by activating the AMPK signaling pathway cascade response, thereby improving IR by regulating glucolipid metabolism, inhibiting inflammatory response, anti-oxidative stress and maintaining mitochondrial homeostasis. Based on this, this paper reviews the pharmacological and experimental research results of TCM intervening the AMPK signaling pathway to improve IR in recent years, expecting to provide reference for further research, development and application of TCM in intervening IR and treating T2DM.

4.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 266-275, 2023.
Article in Chinese | WPRIM | ID: wpr-972309

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance, hyperinsulinemia, and disturbance of glucose and lipid metabolism, with elevated blood glucose as the main clinical manifestation. Due to its complex etiology and pathogenesis, there is no effective treatment, which critically threatens human health and places a heavy burden on society and families. Saponins are a class of glycosides with complex structures that have the advantage of a wide range of sources, elevated safety, and low adverse effects. As an essential active ingredient in Chinese medicine, Chinese medicine saponins have a variety of biological activities such as hypoglycemia, hypoglycaemia, anti-inflammation, antioxidation, anti-tumor, and immune modulation. In recent years, numerous studies have shown that Chinese medicine saponins are effective in preventing and treating T2DM. Although there have been numerous studies on the hypoglycemic effects and mechanisms of Chinese medicine saponins, there has been no systematic review of the mechanisms of Chinese medicine saponins in the treatment of T2DM. Therefore, to provide a theoretical basis for an in-depth study of the hypoglycemic effects of Chinese medicine saponins and a scientific basis for the development and clinical application of drugs, this paper systematically summarized the hypoglycemic mechanisms of Chinese medicine saponins, such as improving islet β-cell function, improving insulin resistance, inhibiting glycosidase activity, reducing the inflammatory response, anti-oxidative stress, and regulating intestinal flora, and analyzed the current research problems and development trends.

5.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 212-223, 2023.
Article in Chinese | WPRIM | ID: wpr-972303

ABSTRACT

Diabetic kidney disease (DKD), a major microvascular complication of diabetes mellitus, serves as the most common cause of end-stage renal disease worldwide. The progression of DKD is closely related to oxidative stress, inflammatory response, apoptosis, and fibrosis in renal tissues activated by high glucose. Numerous studies have shown that the transduction of the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is involved in the pathological process of DKD in renal tissues, activating various pathological mechanisms, such as oxidation, inflammation, apoptosis, and fibrosis. Therefore, blocking the transduction of the p38 MAPK signaling pathway is beneficial to alleviating DKD. At present, the main treatment principles of western medicine are glucose lowering, lipid lowering, and blood pressure lowering, as well as medications with new drugs renal sodium-glucose co-transporter 2 (SGLT2), mineralocorticoid receptor, and endothelin receptor, but the progression of DKD still cannot be stopped. The treatment of DKD by traditional Chinese medicine (TCM) has the advantages of simplicity, low cost, and convenience, and the symptoms and root causes can be both treated. In recent years, the basic research on Chinese medicine intervention in DKD has greatly advanced, and p38 MAPK is the key factor of Chinese medicine intervention in DKD. The present study searched and reviewed the literature on the Chinese medicine intervention in the p38 MAPK signaling pathway in DKD treatment in the past decade. The results showed that p38 MAPK interacted with transforming growth factor-β1 (TGF-β1), cysteinyl aspartate-specific protease-3 (Caspase-3), nuclear factor-κB (NF-κB), and other factors to activate fibrosis, inflammation, oxidative stress, and apoptosis. By acting on p38 MAPK and its upstream and downstream factors, Chinese medicine blocked the pathological processes of DKD and inhibited the pathological injury of DKD and the deterioration of renal function. This study is expected to provide new ideas and directions for the prevention and treatment of DKD with Chinese medicine.

6.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 63-70, 2023.
Article in Chinese | WPRIM | ID: wpr-973133

ABSTRACT

ObjectiveTo investigate the effect of Loulianwan on the gut microbiota of db/db mice with type 2 diabetes mellitus (T2DM). MethodMale db/m+ mice aged 4-5 weeks were assigned to the normal group, and male db/db model mice of the same age were randomly divided into model group, metformin group (0.25 g·kg-1·d-1), and Loulianwan group (13 g·kg-1·d-1), with six mice in each group. Drug intervention lasted five weeks. The body weight, water intake, and fasting blood glucose (FBG) of the mice were recorded every week. After five weeks, the FBG, liver triglyceride (TG), liver total cholesterol (TC), glycated serum protein (GSP), and fasting serum insulin (FINS) were detected, and the insulin resistance index (HOMA-IR) was calculated. The feces in the mouse intestines were collected, and the 16S rRNA sequencing technology was used to detect the structural changes in the fecal gut microbiota of mice in each group. ResultCompared with the normal group, the model group showed increased body weight, water intake, FBG, liver TG, liver TC, GSP, FINS, and HOMA-IR (P<0.01). Compared with the model group, the Loulianwan group showed reduced water intake, FBG, liver TG, liver TC, GSP, FINS, and HOMA-IR (P<0.01). The gut microbiota in the Loulian Lills group changed from phylum to genus level. The relative abundance of beneficial bacteria increased and the relative abundance of harmful bacteria decreased. Among them, the abundance of Akkermansia muciniphila, Blautia, Ruminococcus, and Parabacteroides increased (P<0.01). ConclusionLoulianwan can significantly improve glucose and lipid metabolism in db/db mice with T2DM, and its mechanism may be related to the increase in the abundance of Akkermansia muciniphila, Blautia, Ruminococcus, and Parabacteroides in the intestine.

7.
International Journal of Traditional Chinese Medicine ; (6): 404-409, 2023.
Article in Chinese | WPRIM | ID: wpr-989647

ABSTRACT

Objective:To explore the effectiveness and safety of comprehensive treatment of type 2 diabetes mellitus (T2DM) based on syndrome differentiation and diet.Methods:Prospective clinical study. A total of 147 patients with T2DM from September 2021 to August 2022 who met the inclusion criteria were included in the self-controlled trial. On the basis of diet and exercise intervention, the subjects were treated and observed with comprehensive treatment based on syndrome differentiation for 120 days. The main outcome indicators including TCM symptom score, fasting blood glucose (FPG), 2 hPG, HbA1c , Fasting insulin (FINS), C-peptide(C-PR), and the secondary outcome indicators including blood lipid (TC, TG, HDL-C, LDL-C), blood pressure, and safety indicators were performed before and after treatment.Results:After treatment, the FPG of subjects decreased from (8.75±2.26) mmol/L to (7.05±1.23) mmol/L, 2 hPG decreased from (10.75±3.01) mmol/L to (7.07±0.78) mmol/L, HbA1c decreased from (6.82±1.47)% to (5.49±0.63)%, and FINS decreased from (15.4±9.33) μIU/ml to (8.82±7.28) μIU/ml, C-PR decreases from (1.95±0.91) nmol/L to (1.72±1.53) nmol/L, SBP decreased from (137.51±17.94) mmHg to (125.79±7.57) mmHg, DBP decreased from (82.85±9.65) mmHg to (77.54±6.21) mmHg,TG decreased from (1.57±1.04) mmol/L to (1.25±1.24) mmol/L, HDL-C increased from (1.48±0.41) mmol/L to (1.66±0.46)mmol/L. The above differences were statistically significant ( P<0.05). Conclusion:The comprehensive treatment of T2DM based on syndrome differentiation and diet can significantly reduce the blood glucose indicators including FPG, 2 hPG, HbA1c, FINS and C-PR, and benefit blood pressure and blood lipids with no adverse reactions.

8.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 212-220, 2023.
Article in Chinese | WPRIM | ID: wpr-979467

ABSTRACT

Zishenwan, also known as Tongguanwan, is composed of three herbs:Anemarrhenae Rhizoma, Phellodendri Chinensis Cortex, and Cinnamomi Cortex, which thus is thought to be the representative formula to clear heat, purge fire, nourish Yin, and tonify Qi, and it is often used for treating anuresis and renal arthralgia. In recent years, this formula has become a commonly used combination of herbs and is used to treat diabetes (consumptive thirst disease) diagnosed with "lower consumption" syndrome. This article systematically reviewed the development of traditional Chinese medicine (TCM) theory for Zishenwan. Moreover, based on modern pharmacological research, the previous studies on the components of Zishenwan, the improvement of diabetes-related diseases by Zishenwan, and the relationship between the single herd of Zishenwan and the treatment of diabetes were summarized, and the chemical components and the mechanisms for treating diabetes by the three herbs were discussed. It is found that Zishenwan can alleviate diabetes and diabetic nephropathy by performing anti-inflammation, enhancing insulin sensitivity, and inhibiting pyroptosis of renal tubular epithelial cells. Three herbs in Zishenwan and several components of them, including mangiferin, timosaponins, berberine, jatrorrhizine, cinnamaldehyde, and cinnamic acid can ameliorate diabetes and maintain stable glycometabolism by a variety of mechanisms such as improving insulin resistance in insulin target tissues, suppressing inflammation, anti-oxidation, regulating lipid metabolism, enhancing insulin secretion, and regulating gut microbiota. This review provides a theoretical foundation and reference for subsequent studies on the mechanisms of the anti-diabetic effect of Zishenwan.

9.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 58-64, 2023.
Article in Chinese | WPRIM | ID: wpr-978451

ABSTRACT

ObjectiveTo investigate the effect of modified Huangqi Guizhi Wuwutang (MHGW) on the protein and mRNA expression of B-cell lymphoma-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase-12 (Caspase-12) related to the apoptosis of sciatic nerve cells in diabetes rats to explore the mechanism of MHGW in the treatment of peripheral neuropathy in diabetes. MethodAnimal experiments were conducted. A diabetes model was induced in sixty male sprague-dawley (SD) rats by feeding on a high-sugar and high-fat diet combined with streptozotocin (STZ) intraperitoneal injection. Rats with random blood glucose levels ≥ 16.7 mmol·L-1 for three consecutive days were considered to have successfully developed diabetes. Forty-eight rats that successfully developed diabetes were randomly divided into a model group, an α-lipoic acid group (0.026 8 g·kg-1·d-1), a high-dose MHGW group (2.5 g·kg-1·d-1), and a low-dose MHGW group (1.25 g·kg-1·d-1), with 12 rats in each group. Another 10 rats were assigned to the normal group. Body weight and random blood glucose levels of the rats were monitored. At the end of a 16-week intervention period, the sciatic nerve conduction velocity of the rats was measured using the Key point electromyography collection system. The protein and mRNA expression of Bax and Caspase-12 in the sciatic nerve cells was detected by Western blot analysis and real-time quantitative polymerase chain reaction (Real-time PCR), respectively. ResultCompared with the normal group, the model group showed a significant decrease in body weight (P<0.01) and a significant increase in random blood glucose levels (P<0.01). After a 16-week intervention, compared with the model group, the high-dose MHGW group exhibited a significant increase in body weight (P<0.05), while there were no statistically significant differences in body weight changes among the other treatment groups. Random blood glucose levels significantly decreased in all treatment groups (P<0.01). After 16 weeks of intervention, compared with the normal group, the model group had significantly reduced motor and sensory nerve conduction velocities (P<0.01). Compared with the model group, all treatment groups showed significant increases in motor and sensory nerve conduction velocities (P<0.05, P<0.01). The expression of Bax and Caspase-12 proteins in the sciatic nerve cells was significantly elevated in the model group compared with that in the normal group (P<0.01). In contrast, all treatment groups showed significant reductions in the expression of Bax and Caspase-12 proteins in the sciatic nerve cells as compared with that in the model group (P<0.01). The expression of Bax and Caspase-12 mRNA in the sciatic nerve cells significantly increased in the model group compared with that in the normal group (P<0.01). Compared with the model group, the α-lipoic acid group and the high-dose MHGW group showed significant reductions in the expression of Bax mRNA in the sciatic nerve cells (P<0.05, P<0.01), while the low-dose MHGW group showed a decreasing trend in the expression of Bax mRNA. The expression of Caspase-12 mRNA in the sciatic nerve cells significantly decreased in all treatment groups (P<0.01). ConclusionMHGW may improve and repair sciatic nerve damage in diabetes rats by inhibiting sciatic nerve cell apoptosis.

10.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 43-51, 2023.
Article in Chinese | WPRIM | ID: wpr-978449

ABSTRACT

ObjectiveTo investigate the protective effect of modified Huangqi Guizhi Wuwutang (MHGW) on endoplasmic reticulum stress in the sciatic nerve of diabetes rats based on the pathways of inositol-requiring enzyme 1α (IRE1α) and CCAAT/enhancer-binding protein homologous protein (CHOP). MethodSixty rats were fed on a high-sugar and high-fat diet for six weeks, followed by intraperitoneal injection of streptozotocin at a dose of 35 mg·kg-1. Random blood glucose levels were measured three days later and rats with a sustained blood glucose level ≥ 16.7 mmol·L-1 were included in study (n=48). The rats were randomly divided into a model group, an α-lipoic acid group (0.026 8 g·kg-1·d-1), a high-dose MHGW group (2.5 g·kg-1·d-1), and a low-dose MHGW group (1.25 g·kg-1·d-1). Another 10 rats were assigned to the normal group. The intervention lasted for 16 weeks. After 16 weeks, the sciatic nerve structure of the rats in each group was observed under light microscopy using Luxol fast blue (LFB) staining. Transmission electron microscopy was used to observe the ultrastructure of the sciatic nerve. Chemiluminescence method was employed to measure the serum reactive oxygen species (ROS) levels. Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to evaluate the expression of p-IRE1α protein, IRE1α mRNA, CHOP protein, and CHOP mRNA in the sciatic nerve of the rats. ResultCompared with the normal group, the model group showed elevated serum ROS levels (P<0.01). In contrast, the serum ROS levels were significantly reduced in the treatment groups compared with those in the model group (P<0.01). The sciatic nerve of the model group showed pathological changes compared with that in the normal group, while the treatment groups exhibited improvement in sciatic nerve pathology compared with the model group. The protein expression of p-IRE1α and CHOP in the sciatic nerve significantly increased in the model group as compared with that in the normal group (P<0.01). However, the treatment groups showed a significant decrease in the protein expression of p-IRE1α and CHOP in the sciatic nerve compared with the model group (P<0.05, P<0.01). Furthermore, compared with the normal group, the model group showed upregulated mRNA expression of IRE1α and CHOP in the sciatic nerve (P<0.01), while the treatment groups exhibited a significant decrease in the mRNA expression of IRE1α and CHOP compared with the model group (P<0.01). ConclusionMHGW can alleviate endoplasmic reticulum stress-induced cell apoptosis and improve the structure and function of the sciatic nerve in diabetes rats by inhibiting the expression of IRE1α/CHOP pathway-related proteins and mRNA, thereby preventing and treating peripheral neuropathy in diabetes.

11.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 22-32, 2023.
Article in Chinese | WPRIM | ID: wpr-978447

ABSTRACT

ObjectiveTo explore the effect of Zishenwan on glucose and lipid metabolism in spontaneous type 2 diabetes (db/db) mice and investigate the underlying mechanism for improving diabetes based on intestinal barrier function and skeletal muscle transcriptome sequencing results. MethodLiquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the components of Zishenwan. Sixteen 6-week-old db/db mice were divided into a model group and a Zishenwan group, while eight wild-type mice were assigned to the normal group. The Zishenwan group received oral administration of drugs for six weeks, during which fasting blood glucose, body weight, and food intake were measured. Serum total cholesterol (TC) and triglyceride (TG) levels were determined, and fasting insulin levels were measured to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). After the treatment, skeletal muscle and ileum tissues were collected, followed by hematoxylin-eosin (HE) staining. Immunohistochemistry was used to detect the expression of tight junction proteins occludin and zonula occludens-1 (ZO-1) in the ileum. Transcriptome sequencing was performed to detect the skeletal muscle transcriptome, and enrichment analysis was conducted for differentially expressed genes. ResultMultiple active components were identified in Zishenwan. Compared with the normal group, the model group showed increased fasting blood glucose, body weight, TC, TG, and HOMA-IR (P<0.01). Compared with the model group, Zishenwan significantly reduced fasting blood glucose, body weight, TC, TG, and HOMA-IR in db/db mice (P<0.01), while there was no statistically significant difference in food intake. Compared with the normal group, the model group exhibited lipid deposition in skeletal muscle, as well as structural changes in the ileum, with significant decreases in the protein expression levels of intestinal occludin and ZO-1 (P<0.01). Compared with the model group, Zishenwan improved the pathological changes in skeletal muscle and ileum, and increased the protein expression of occludin and ZO-1 in the ileum (P<0.01). Transcriptome analysis suggested that Zishenwan might improve skeletal muscle metabolism and increase insulin sensitivity in mice. ConclusionZishenwan can improve glucose and lipid metabolism in db/db mice, and this effect may be related to its protection of intestinal barrier function and transcriptional regulation of skeletal muscle metabolism-related genes.

12.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 263-271, 2023.
Article in Chinese | WPRIM | ID: wpr-953948

ABSTRACT

Diabetic nephropathy (DN), the most feared microvascular complication of diabetes and one of the most common and serious complications of diabetes, is the major cause of end-stage renal disease worldwide, leading cause of morbidity and mortality in patients with diabetes, and the main non-communicable cause of death worldwide. There are many types of saponins, which are the main bioactive components of various Chinese medicinals. They have various pharmacological activities such as lowering blood glucose and blood lipids, improving insulin resistance, anti-inflammation, anti-oxidative stress, anti-tumor, and immune modulation. In recent years, it has been frequently verified that the saponins in Chinese medicinals have definite effect in regulating DN, showing multi-target, multi-pathway, multi-system, multi-effect characteristics. Thus, they have broad prospects in the prevention and treatment of this disease. There has been an explosion of research on the treatment of DN with saponins in Chinese medicinals in vivo and in vitro, but there is a lack of systematic and comprehensive summary. Therefore, this study summed up the studies of saponins in Chinese medicinals in the intervention of DN and summarized the mechanisms such as improving glucolipid metabolism, inhibiting oxidative stress, anti-inflammation, anti-apoptosis, regulating autophagy, anti-fibrosis, and protecting podocytes, with a view to providing ideas and references for the development of drugs related to DN.

13.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 99-108, 2023.
Article in Chinese | WPRIM | ID: wpr-965653

ABSTRACT

Diabetic peripheral neuropathy (DPN) is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN, one of the most common complications of diabetes mellitus, can lead to disability, foot ulcers, and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage, oxidative stress, mitochondrial disorders, and apoptosis in neural tissues. The p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is a key mechanism mediating the expression of inflammatory factors, oxidative factors, and apoptotic factors of neural tissues in DPN. The inflammatory response, oxidative stress damage, and apoptosis, induced by the activation of p38 MAPK phosphorylation by factors such as high glucose, can cause cell lipid peroxidation, protein modification, and nucleic acid damage, which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years, the research on traditional Chinese medicine (TCM) in the prevention and treatment of DPN has gradually increased, and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN, such as inflammation regulation, oxidative stress, polyol pathway regulation, and Schwann cell apoptosis in the past 10 years. In addition, the literature on Chinese medicine monomers, Chinese patent medicines, and Chinese medicine compounds in inhibiting inflammatory reactions, oxidative injury, and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway, resisting axonal degeneration and demyelination changes, improving sensory and motor abnormalities, relieving peripheral pain sensitization, and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.

14.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 91-98, 2023.
Article in Chinese | WPRIM | ID: wpr-965652

ABSTRACT

ObjectiveTo explore the effect of Tangbikang granules (TBK) on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor (NF)-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin (STZ, ip) at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group, low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK groups, and lipoic acid group (0.026 8 g·kg-1) according to body weight and blood glucose level, and a normal group was designed. After modeling, administration began and lasted 12 weeks. The body mass, blood glucose level, and thermal withdrawal latency (TWL) of the rats were detected before treatment and at the 4th, 8th, and 12th week of administration. At the 12th week, the sciatic nerve was collected for hematoxylin-eosin (HE) and Luxol fast blue (LFB) staining, and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in sciatic nerve were measured by enzyme-linked immunosorbent assay (ELISA), and the levels of AMPK, phosphorylated (p)-AMPK, and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point (P<0.01). The levels of IL-1β, TNF-α, and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group (P<0.01), and the p-AMPK/AMPK ratio was smaller than that in the normal group (P<0.01). Compared with the model group, TBK of the three doses lowered the TWL (P<0.05, P<0.01) and the levels of IL-1β, TNF-α, and NF-κB protein in sciatic nerve of rats (P<0.05, P<0.01), and high-dose and medium-dose TBK raised p-AMPK/AMPK (P<0.05, P<0.01). The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB, thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.

15.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 81-90, 2023.
Article in Chinese | WPRIM | ID: wpr-965651

ABSTRACT

ObjectiveTo explore the mechanism of Tangbikang granules (TBK) against diabetic peripheral neuropathy (DPN) based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME, the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN, which were uploaded to Metascape for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin (STZ, ip) were employed to induce diabetes in rats, and then the model rats were respectively treated with low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK for 12 weeks. Sensory nerve conduction velocity (SNCV) was evaluated. After hematoxylin and eosin (HE) staining, the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase (AMPK) pathway-related targets in rat sciatic nerve, and Western blot to measure the protein expression of AMPK and phosphorylated (p)-AMPK in rat sciatic nerve. ResultThe main active components of TBK, such as quercetin, kaempferol, β-sitosterol, leech pteridine A, stigmasterol, and baicalein were screened out, mainly acting on interleukin-6 (IL-6), tumor necrosis factor (TNF), protein kinase B (Akt), JUN, and HSP90AA1 and signaling pathways such as AMPK, nuclear factor-κB (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6, TNF, JUN, and HSP90AA1. As for the animal experiment, compared with the normal group, model group had low SNCV of sciatic nerve (P<0.01), disordered and loose myelinated nerve fibers with axonotmesis and demyelinization, low mRNA expression of AMPKα, AMPKβ, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Sirtuin 3 (SirT3), mitochondrial transcription factor A (TFAM), and low p-AMPK/AMPK ratio in sciatic nerve (P<0.05, P<0.01). Compared with the model group, TBK of the three doses raised the SNCV (P<0.01), restored nerve morphology and nerve compactness, and increased the mRNA expression of AMPKα, AMPKβ, PGC-1α, SirT3, and TFAM (P<0.05, P<0.01). The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group (P<0.01), while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling, which lays a basis for further study of TBK in the treatment of DPN.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 71-80, 2023.
Article in Chinese | WPRIM | ID: wpr-965650

ABSTRACT

ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules(TBK) on type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats, which were then respectively treated (ig) with low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK for 12 weeks. Fasting blood glucose (FBG) and body mass were recorded every 4 weeks during the treatment. One week before sampling, the feed intake of rats was detected, and after 12 h night fasting, oral glucose tolerance test (OGTT) was performed. The area under the curve (AUC) was used to evaluate glucose tolerance, and the homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes: Fasting serum insulin (FINS), serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and nonesterified fatty acids (NEFA). The liver was weighed to calculate the liver index, and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The protein levels of insulin receptor substrate (IRS), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group (P<0.01), and the feed intake the administration groups was lower than that in the model group (P<0.05, P<0.01). At the 8th and 12th week, the body mass in the model group was lower than that in the normal group (P<0.01). Compared with the model group, TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group (P<0.01). The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group, and AUC in the administration groups was significantly different from that in the model group (P<0.01). The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group (P<0.01), and they were lower in the TBK groups than in the model group (P<0.01). Serum levels of TG, TC, HDL-C, NEFA (P<0.05, P<0.01), and LDL-C were higher in the model group than in the normal group. Serum levels of TG, TC, LDL-C, and NEFA in the TBK groups were lower than those in the model group, and the levels of TG, LDL-C, and NEFA in TBK groups were concentration-dependent (lowest levels in high-dose TBK group). Compared with the model group, high-dose TBK significantly increased the level of HDL-C (P<0.05). Liver index of the model group was higher than that in the normal group (P<0.01). The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver, the model group had unclear structure of liver lobule, enlarged cells of different sizes, and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury, particularly the high dose. For the PAS staining, compared with the normal group, the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein, p-IRS1/IRS1, and p-Akt/Akt in the model group were lower than those in the normal group (P<0.01), and they were higher in the high-dose TBK group than in the model group (P<0.01). ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.

17.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 42-49, 2022.
Article in Chinese | WPRIM | ID: wpr-940759

ABSTRACT

ObjectiveTo investigate the effect of Chuanshanlong granule on Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear transcription factor -κB (NF-κB) signaling pathway, and to explore the mechanism of its treatment of autoimmune thyroiditis (AIT) in rats. MethodForty AIT models were established following excess iodine and injection of porcine thyroglobulin and Freund's adjuvant into Lewis rats for six weeks. Then the rats were randomly divided into the model group, Chuanshanlong granule low-, medium- and high-dose group (0.52, 1.03, 2.06 g·kg-1·d-1), with ten in each group. Rats in the Chuanshanlong granule low-, medium- and high-dose groups were separately given 0.01 mL·g-1·d-1 Chuanshanlong granule, and those in the normal group and the model group were given the same volume of deionized water for eight weeks. Serum of rats was taken to measure thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) by enzyme-linked immunosorbent assay (ELISA), and the concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were detected. The rat thyroid lobes were stained with hematoxylin and eosin (HE), and the pathological changes were observed under light microscope. In addition, the relative expression of TLR4, MyD88, NF-κB protein and mRNA was determined by immunohistochemistry and real-time polymerase chain reaction (Real-time PCR). ResultCompared with the conditions in the normal group, the serum concentrations of TPOAb and TgAb (P<0.01) and FT3 and FT4 (P<0.01) increased and TSH decreased (P<0.01) in the model group. Compared with the conditions in the model group, the concentrations of TPOAb and TgAb in the Chuanshanlong granule treatment groups reduced (P<0.01), and the concentrations of FT3 and FT4 were lowered (P<0.01) while TSH increased (P<0.01) in the Chuanshanlong granule high-dose group. HE staining showed that there was lymphocyte infiltration in the thyroid follicular space, a large number of destroyed or diminished follicular cavities, decreased colloid content, and thinned or destroyed follicular wall in the model group, while the thyroid lymphocyte infiltration in the Chuanshanlong granule treatment groups was significantly less and the structure of thyroid follicles was more complete than those in the model group. Compared with the normal group, the model group had up-regulated relative expression of TLR4, MyD88 and NF-κB protein (P<0.01) and mRNA (P<0.01). Compared with the model group, the Chuanshanlong granule high-dose group had down-regulated relative expression of TLR4 protein and mRNA (P<0.05), MyD88 protein (P<0.01) and mRNA (P<0.05), and NF-κB protein and mRNA (P<0.01). ConclusionChuanshanlong granule may play a therapeutic role in AIT by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.

18.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 42-49, 2022.
Article in Chinese | WPRIM | ID: wpr-943082

ABSTRACT

ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O1 (FoxO1) signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group, and KKAy male mice of the same age were randomly assigned into a model group, a metformin group, Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 (Trichosanthis Radix 30 g, Polygonati Rhizoma 30 g), 1∶3 (Trichosanthis Radix 15 g, Polygonati Rhizoma 45 g), and 1∶5 (Trichosanthis Radix 10 g, Polygonati Rhizoma 50 g) according to blood glucose level and body weight, with 6 mice in each group. The administration lasted for 8 weeks, and the body weight (BW) and fasting blood glucose (FBG) of mice were recorded at the same time points of the 2nd, 4th, 6th, and 8th weeks, respectively. Oral glucose tolerance test (OGTT) was performed at the 7th week. After drug administration, the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting insulin (FINS) were measured, and homeostasis model assessment-insulin resistance (HOMA-IR) index was calculated. The liver tissue samples were stained with hematylin-eosin (HE) and periodic acid-Schiff (PAS) for observation of the fat distribution and glycogen content. The protein levels of PI3K, Akt, p-Akt, FoxO1, and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group, the model group showed increased food intake, FBG, glucose tolerance, FINS, HOMA-IR, TC, TG, and LDL-C (P<0.01), and down-regulated protein levels of PI3K, Akt, phosphorylaison (p)-Akt, FoxO1, and p-FoxO1 in the liver (P<0.01). Compared with the model group, Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR (P<0.05, P<0.01). In particular, the combination at the ratio of 1∶3 showed the best performance (P<0.01) comparable to metformin. Furthermore, Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT (P<0.05) and TC and LDL-C (P<0.01). Additionally, the combination at the ratio of 1∶3 reduced TG (P<0.01). The liver of mice in the drug administration groups showed regular morphology, with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt, down-regulated the protein level of FoxO1, and up-regulated the protein level of p-FoxO1 (P<0.05). ConclusionTrichosanthis Radix-Polygonati Rhizoma, especially at the ratio of 1∶3, lowered the FBG, TC, LDL-C, and HOMA-IR index, promoted liver glycogen synthesis, and reduced steatosis in KKAy mice, which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.

19.
International Journal of Traditional Chinese Medicine ; (6): 1358-1364, 2022.
Article in Chinese | WPRIM | ID: wpr-954467

ABSTRACT

Objective:To observe the clinical effects of Traditional Chinese Medicine (TCM) Tangnaikang granules, supplementing to conventional treatment methods, on type 2 diabetic foot ulcer.Methods:A total of 67 patients, from Beijing University of Chinese Medicine subsidiary Dongfang Hospital, Tuanjie Lake Community Health Service Center, Qingta Community Health Service Center between August, 2019 and November, 2020 were assigned to treatment group (37 patients) and control group (30 patients) using sealed envelope randomization method. The control group underwent conventional treatment methods that manage blood sugar and treat infections. The treatment group received, in addition to the conventional treatment methods administered to the control group, Tangnaikang granules. Both groups were continuously treated for 90 days. The TCM symptom scores, granulation tissue scores, visual analogue scale (VAS), itching scores and Generic Quality of Life Inventory-74 (GQOL-74) score, wound area were observed pre- and post-treatment. The ELISA kits were used to detect the Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Basic Fibroblast Growth Factor (bFGF), fasting blood glucose level, glycated hemoglobin test (HbA1c), fasting insulin level, postprandial 2 hour insulin level, insulin resistance index. And all possible adverse events were noted. The overall clinical treatment effects and TCM symptom treatment effects were assessed.Results:Total effective rate for the treatment group 89.2% (33/37), was significantly different from that of the control group 70.0% (21/30) with χ2=3.90 and P<0.01. The TCM symptom effective rate was 86.5% (32/37) for the treatment group and 63.3% (19/30) for the control group. The difference was statistically different with χ2=4.88 and P<0.01. After treatment, whole blood viscosity, plasma viscosity, fibrinogen and erythrocyte sedimentation rate (ESR) of the treatment group were significantly improved than those of the control group ( t=-23.38, -8.01, 18.10, -18.93,all Ps<0.01). The ulcer closure area (5.43±1.65 cm 2vs. 4.65±1.14 cm 2, t=2.20) and ulcer closure area percentage (59.14%±3.37% vs. 42.42%±3.21%, t=20.63) were statistically different of both groups ( P<0.05 or P<0.01). The VEGF, EGF, and bFGF at 90 day of the treatment group were significantly higher than those of the control group ( t=3.19, 40.59, 28.53, all Ps<0.01). The post-treatment fasting blood glucose level, insulin resistance index of the treatment group were significantly lower than those of the control group ( t=-8.55, -21.38, all Ps<0.01). TCM symptoms of thirsty, feverish sensation in chest, palms and soles in the treatment group were significantly improved than the control group ( χ2=4.38, 4.48, all Ps<0.01). Conclusion:TCM compound Tangnaikang granules can relieve diabetic foot ulcer, reduce wound healing time and improve overall treatment outcome, when it was combined of the conventional treatment.

20.
International Journal of Traditional Chinese Medicine ; (6): 431-436, 2020.
Article in Chinese | WPRIM | ID: wpr-863623

ABSTRACT

Objective:To observe the clinical efficacy of Shenqi-Dihuang Decoction combined with conventional western medicine in the treatment of stage Ⅳ Diabetic Nephropathy (DN). Methods:Made a retrospective analysis of 80 patients of stage Ⅳ DN with the syndrome of qi and yin deficiency combined with blood stasis from June 2017 to June 2018, from Beijing Hospital of Traditional Chinese Medicine and The Third Affiliated Hospital of Beijing University of Chinese Medicine. The 80 patients were divided into treatment group and control group, 40 in each group. The control group was given the conventional western treatment. The treatment group was given Shenqi-Dihuang Decoction on the basic of the control group. Both of the treatments for the two groups lasted for 12 weeks. Before and after the treatment, the changes of TCM syndrome scores were observed in each group. The automatic biochemical analyzer was used to detect the level of fasting plasma glucose, 2-hour postprandial glucose (2 hPG), Boold Urea Nitrogen (BUN), Serum Creatinine (SCr), Plasma Albumin (Alb), Total Cholesterol (TC), Triglyceride (TG), Uric Acid (UA), Superoxide Dismutase (SOD), Homocysteine (HCY) before and after treatment. The Glycosylated Hemoglobin Alc were measured by high performance liquid chromatographic (HPLC), 24-hour urine total protein quantity (24 hUTP) were measured by immunoturbidimetric assay before and after treatment, and then Glomerular Filtration Rate (eGFR) was estimated to evaluate clinical effect. Results:After the treatment, the total effective rate in the treatment group was 87.5% (35/40), and the control group was 67.5% (27/40) and the difference was statistically significant ( χ2=4.557, P=0.033). After the treatment, the scores of urine turbid, weakness of waist and knees, fatigue, edema of both lower limbs were decreased in both groups, and the treatment group was significantly better than those of the control group ( t value were -2.178, -1.675, -3.667, -1.904, -4.835, respectively, all Ps<0.01). After the treatment, the level of FPG and HbA1c were significantly lower than those of the control group ( t value were-3.781, -8.557, respectively, all Ps<0.01); the systolic blood pressure was significantly lower than that of the control group ( t=-2.883, P=0.005); the level of TC was significantly lower than that of the control group ( t=-3.321, P=0.008); the level of Alb was significantly higher than that of the control group ( t=1.510, P=0.367); the level of 24 hUTP was significantly lower than that of the control group ( t=-2.819, P=0.008); the level of HCY were significantly lower than that of the control group ( t=-2.053, P=0.043); the level of SOD was significantly higher than that of the control group ( t=2.849, P=0.018). Conclusions:Shenqi-Dihuang Decoction combined with conventional western medicine can reduce 24 hUTP quantity of Ⅳ DN patients with the syndrome of qi and yin deficiency combined with blood stasis, reduce kidney damage, delay the development of Ⅳ DN, improve clinical effect and protect the kidney function.

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