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1.
Article in Chinese | WPRIM | ID: wpr-872780

ABSTRACT

A good neural microenvironment is an important basis for improving the damaged nerves and promoting axonal repair and regeneration. The destruction of neural microenvironment, closely related to the lack of neurotrophic factors, microcirculation disorders and immune abnormalities, is the key pathogenesis leading to diabetic peripheral neuropathy (DPN). In traditional Chinese medicine, disharmony between Ying and Wei is considered as the key pathology in the development of DPN. It may be manifested as Ying and Wei deficiency, or Ying and Wei impassability, or Ying, Wei, Qi and blood intersection disorders, all of which may cause body fluid condensed into phlegm, blood into blood stasis, further leading to the mutual knot of phlegm and blood stasis, meridian obstruction, numbness and pain of limbs. "Regulating Ying and Wei and tonifying spleen and stomach" is the main therapeutic idea to promote intersection between Ying and Wei and unblock Qi and blood. The method has a significant effect on DPN. However, the current studies on the mechanism of regulating Ying and Wei in the treatment of DPN are still in lack of in-depth discussion, and the studies are mostly limited to the microcirculation disorders. Numerous studies have confirmed that the courses and distribution, physiological characteristics, functions of Ying and Wei are closely related to nerve, immune, metabolic substances and microcirculation. Based on the modern medicine essence of Ying and Wei, the author thinks that the discussion on connotation of the Ying and Wei from the perspective of neural microenvironment has a scientific basis, and regulating Ying and Wei is not only inherited from the traditional Chinese medicine theory, but also conforms to the modern understanding on DPN pathogenesis and treatment. Regulating Ying and Wei and smoothing middle-jiao can improve neural microenvironment and give play to the role of restoring damaged nerve, and its mechanism may be related to regulating neurotrophic factors, immune active substances, metabolites, and microcirculation dysfunction.

2.
Article in Chinese | WPRIM | ID: wpr-872726

ABSTRACT

Objective:To explore the effect of Shenqi compound on islet β-cell function in type 2 diabetic GK rats. The whole genome expression profile chip technology is used to explore the molecular mechanism of Shenqi compound regulating pancreatic islet cell function and provide theoretical basis for the prevention and treatment of type 2 diabetes with traditional Chinese medicine. Method:GK rats were fed with high-fat diet daily for 4 weeks. Rats were randomly selected from GK rats to detect random blood glucose and verified the success of type 2 diabetes model. Rats were divided into 4 groups, Wistar group, model group, Shenqi compound(1.44 g∙kg-1) group and west glenn(16 mg∙kg-1) group. After 8 weeks of gavage, the serum insulin(INS) levels were detected by enzyme-linked immunosorbent assay(ELISA). The apoptosis of islet β cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)fluorescence method. Differential gene detection uses whole-genome expression profiling chip technology in each group of rat pancreatic tissues, the mRNA transcription level of key differential genes is detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR). Result:Compared with blank group, before gavage, 4 weeks, 8 weeks, GK rats have higher blood sugar in each group (P<0.01).Gavage for 4 weeks and gavage for 8 weeks, compared with model group, the blood sugar of rats in each drug intervention group was lower (P<0.01). Gavage for 8 weeks, compared with blank group, the INS level of model group was lower (P<0.01). Compared with model group, the Shenqi compound group had a higher INS level, and the sitagliptin group had a higher INS level (P<0.01). After gavage for 8 weeks, compared with the blank group, the number of pancreatic islet β-cell apoptosis in the model group was higher (P<0.05). Compared with model group, the number of pancreatic islet β cell apoptosis in the Shenqi compound group and sitagliptin group was lower (P<0.05,P<0.01). Gene chip and Real-time PCR tests both showed that phosphatidylinositol 3-kinase receptor 1(PIK3R1) was up-regulated in the Shenqi compound group/model group, and down-regulated in the sitagliptin group/model group, model group/blank group. Protein kinase B1(Akt1) was expressed in the Shenqi compound group/model The expression was up-regulated in the group, sitagliptin group/model group, and down-regulated in the model group/blank group. Conclusion:Shenqi compound which has the function of supplenmenting Qi and Yin and promoting the blood circulation, can inhibit the islet β cell apoptosis, improve islet β cell function, regulate insulin secretion, and prevent T2DM by up-regulating the expression of genes PIK3R1 and Akt1.

3.
Article in Chinese | WPRIM | ID: wpr-801851

ABSTRACT

The gut microbiota and its metabolites play a critical role on health maintenance, because they are involved in the absorption and metabolism of nutrients in the human bodies. This is also similar to traditional Chinese medicine (TCM) view that the ascending and descending of Qi movement affects Yin-Yang, Qi-blood, pneuma and body fluid, viscera and meridians of our bodies. More and more studies have demonstrated that gut microbiota is closely related to the development and progression of diabetes and its complications. Gut microbiota disorder could affect host metabolic signaling pathways, thereby promoting the formation and development of diabetes. The smooth ascending and descending of Qi movement is the basic form of maintaining host metabolic homeostasis, whose dysfunction however can lead to internal environment disturbance. Based on the theory of ascending and descending of Qi movement, this paper focuses on the pathogenesis of imbalanced intestinal flora in the process of the induction of diabetes mellitus from a dynamic perspective. It is assumed that the imbalance of Qi ascending and descending may act as a trigger for such symptoms as lung Qi impairment, spleen deficiency to dissipating essence, liver Qi stagnation and kidney Yang deficiency. Under this circumstance, gut microbiota will be out of balance, which will further lead to the nutrient substance metabolic disturbance in the body, and thus induce diabetes. Thus, it is significant to explore the regulatory mechanism of gut microbiota and its metabolites on diabetes based on the theory of ascending and descending of Qi movement, so as to reveal the scientific connotation of TCM in regulating substance metabolism homeostasis in the body.

4.
Article in Chinese | WPRIM | ID: wpr-801801

ABSTRACT

Objective: To observe the effect of Shenqi compound recipe on glucose and lipid metabolism in patients with Qi and Yin deficiency and blood stasis syndrome newly diagnosed type 2 diabetes mellitus (T2DM), and its intervention effect on intestinal microecology and serum proinflammatory factors. Method: The 106 eligible patients were divided into the observation group (54 cases) and the control group (52 cases) by random number table method. Another 40 healthy volunteers in physical examination center of the hospital during the same period were enrolled as health control group. On the basis of Guidelines for the Prevention and Treatment of Type 2 Diabetes in China(2013 edition), control group was provided lifestyle interventions, such as reasonable diet, weight control, moderate exercise, salt restriction, tobacco control, alcohol restriction and psychological balance. In addition to the therapy of the control group, the observation group was given Shengi compound for oral administration, 2 times/days. Both groups were treated for 8 weeks. The fasting blood glucose (FBG), postprandial 2 h blood glucose (PBG), glycosylated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance index (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) before and after treatment were evaluated. The structure and quantity of intestinal flora before and after treatment were detected. The traditional Chinese medicine(TCM)symptom was scored. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α) were measured before and after treatment. Result: FBG, PBG, HbA1c and HOMA-IR levels in observation group were lower than those in control group (PPPPβ, IL-6, IL-8 and TNF-α levels in observation group were lower than those in control group (PZ=2.134, PConclusion: Shenqi compound can regulate blood glucose and blood lipid in patients with newly diagnosed T2DM (Qi and Yin deficiency and blood stasis syndrome), improve IR, intestinal microecology imbalance, and reduce non-specific inflammatory response, with a good clinical efficacy on intestinal microecology of patients with Qi and Yin deficiency and blood stasis syndrome newly diagnosed type 2 diabetes mellitus.

5.
Article in Chinese | WPRIM | ID: wpr-798519

ABSTRACT

Reducing glycemic excursion is of great importance to the successful practice for diabetes intervention and complication prevention. This is also an advantage of traditional Chinese medicine (TCM) in the treatment of diabetes. More and more studies have shown that the dysfunction of islet microcirculation is the key pathological link for glycemic excursion caused by decrease of islet function. The over-activation of local renin-angiotensin system (RAS) in islet microcirculation is a key ring to the islet decompensation, intimately related to the functionality of islet endocrine cells, and has gradually become the focus in the study of islet functionality. In TCM, it is believed that glycemic excursion in diabetes mellitus is closely related to the incapability of "spleen Qi to dispersing essence". If spleen fails to disperse essence, the essence will be accumulated in the body and become harmful stuffs. The stuffs further break the blood glucose homeostasis, acting as the key pathogenesis of diabetes. By supplementing the "spleen" Qi and promoting the dispersion of nutrient substance (hormone) in "pancreas", the balance between sugar-regulated hormones can be restored and therefore glycemic excursion can be reduced. However, the regulation mechanism of "spleen Qi to dispersing essence" on glycemic excursion remains unclear at present. Based on the previous clinical and scientific work, the following ideas were proposed by the authors:the effects of "spleen Qi to dispersing essence" on the improvement of islet function and the regulation of glycemic excursion may be achieved by promoting islet microcirculation, and its mechanism may be related to inhibiting the activation status of local RAS in islet microcirculation. It is important to note that the mutual antagonistic relationship between the signal pathways of RAS in islet microcirculation is similar to the antagonistic relationship between "spleen Qi to dispersing essence" and spermatozoa in TCM. Thus, the mechanism of "spleen Qi to dispersing essence" on the regulation mechanism of blood glucose fluctuations needs to be further explored from the perspective of the overall regulation of RAS in islet microcirculation, so as to reveal the scientific connotation of TCM on regulating the body's environmental homeostasis and reducing glycemic excursion in diabetic patients.

6.
Journal of Medical Postgraduates ; (12): 1192-1195, 2018.
Article in Chinese | WPRIM | ID: wpr-818009

ABSTRACT

The metabolic memory formed by early hyperglycemia in diabetes is one of the important factors triggering the development of diabetes and relavant complications. At present, treatment of various adverse factors of metabolic memory shows a limited clinical efficacy. In recent years, exosome emerged as an important mediator of cellular communication and have gradually gained importance attendance in the field of diabetes treatments. This review summarizes the main mechanisms involved in the metabolic memory of exosomes in the pathological state, including inflammation, insulin resistance, oxidative stress and apoptosis. In addition, protection mechanisms of the stress pretreatment and stem cells derived exosomes on metabolic memory are discussed in this review. Finally, the possible ways to obtain therapeutic exosomes are elaborated, which is beneficial to generate new ideas for the clinical drug treatment.

7.
Article in Chinese | WPRIM | ID: wpr-294342

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats.</p><p><b>METHODS</b>Totally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05).</p><p><b>CONCLUSIONS</b>Shenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.</p>


Subject(s)
Animals , Collagen Type I , Metabolism , Collagen Type III , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Diabetic Angiopathies , Drugs, Chinese Herbal , Pharmacology , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Metabolism , p38 Mitogen-Activated Protein Kinases , Metabolism
8.
Article in Chinese | WPRIM | ID: wpr-287556

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of Shenqi Compound (SQC) on the mRNA expression of angiotensin II type 1 receptor (AT1R) in the aorta of Goto-Kakizaki (GK) rats.</p><p><b>METHODS</b>Totally 67 GK rats were randomly divided into 5 groups, i.e., the GK group (n =18), the model group (n =16), the atorvastatin group (n =17), and the SQC group (n =16). Another a normal control group was set up (n =18). The diabetic macrovascular disease model was prepared by adding L-NAME (at the daily dose of 0.10 mg/mL) in drinking water for GK rats. GK rats, except those in the normal control group were fed with high fat diet. Atorvastatin (at the daily dose of 1.60 mg/kg) and SQC (at the daily dose of 1.44 g/kg) were respectively administered by gastrogavage, once daily for 35 successive days. The blood glucose was determined by glucose oxidase method once per week. After 5-week medication, the contents of triglyceride (TG) and total cholesterol (TC) were determined by ELISA. The serum concentrations of angiotensin I (Ang II) were determined by RIA. The mRNA expression of AT1R in the aorta was determined by real-time quantitative reverse transcriptase PCR (RT-PCR).</p><p><b>RESULTS</b>The blood glucose level was obviously lower in both the atorvastatin group and the SQC group after 4 weeks of medication (P <0.05). Besides, it was significantly lower in the SQC group than in the model group by the end of the 4th week (P <0.05). The concentrations of TG, TC and serum Ang II , and the mRNA expression of AT1R in the aorta were significantly higher in the model group than in the normal control group (P <0.01). After 5-week medication, the concentrations of TG, TC and serum Ang I , and the mRNA expression of AT1 R in the aorta were significantly lower in the atorvastatin group and the SQC group than in the model group (P <0.01, P <0.05). The mRNA expression of AT1R was significantly higher in the SQC group than in the atorvastatin group (P <0.05).</p><p><b>CONCLUSIONS</b>SQC could significantly reduce the levels of blood glucose, TG, TC, down-regulate the mRNA expression of AT1R in the aorta, and decrease the expressions of serum Ang II of GK rats with diabetic macrovascular disease. AT1 R might be one of effective targets of SQC in treating diabetic macrovascular diseases.</p>


Subject(s)
Angiotensin II , Blood , Animals , Aorta , Metabolism , Blood Glucose , Cholesterol , Blood , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacology , Male , RNA, Messenger , Genetics , Rats , Receptor, Angiotensin, Type 1 , Genetics , Metabolism , Triglycerides , Blood
9.
Article in Chinese | WPRIM | ID: wpr-313231

ABSTRACT

<p><b>OBJECTIVE</b>To research the effects and mechanism of Shenqi compound (SQC) on PTEN/ PI3K signal transducing path and angiogenesis in Goto-Kakizaki (GK) rats with diabetes mellitus type 2 (DM2) caused macroangiopathy.</p><p><b>METHOD</b>GK rats with blood sugar > or = 11.1 mmol/L were divided into 4 groups, the GK group, the model group, the Western medicine (WM) group treated by atorvastatin 1.5 mg/(kg x d) and the Chinese medicine (CM) group treated with SQC 1.44 g/(kg x d). All were fed 35 days with high fatty diet, but to the latter three groups, N omega-nitriyl-L-arginine methyl ester 0.1 mg/mL was added into their drinking water for macroangiopathy model establishing. Besides, a group of normal Wistar rats fed with ordinary forage was set for control. Rat's blood glucose and lipids were measured, morphology of abdominal aorta wall tissue was observed with HE staining, and mRNA expressions of PTEN and PI3Kp85 in aortic wall were detected by Real-time PCR.</p><p><b>RESULTS</b>General condition, gluco-lipid metabolism and aortic morphology in the CM group were significantly better than those in the model group. PTEN mRNA expression in the CM group (1.10 +/- 0.48) was significantly higher than that in the GK group (0.63 +/- 0.16) and the model group (0.17 +/- 0.07, both P < 0.01), but near to that in the WM group (1.11 +/- 0.46), while the PI3Kp85 mRNA expression in the TCM group (0.19 +/- 0.05) was lower than that in the GK group (1.38 +/- 0.43, P < 0.01), but near to that in the model group (0.33 +/- 0.09) and the WM group (0.11 +/- 0.06, both P > 0.05).</p><p><b>CONCLUSION</b>SQC could increase the PTEN mRNA expression and restrain the PI3Kp85 mRNA expression in aorta, which is possibly the partial mechanisms of action of the remedy in inhibiting angiogenesis and preventing diabetic macroangiopathy.</p>


Subject(s)
Angiogenesis Inhibitors , Pharmacology , Therapeutic Uses , Animals , Aorta , Metabolism , Astragalus propinquus , Chemistry , Atherosclerosis , Class Ia Phosphatidylinositol 3-Kinase , Genetics , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Diabetic Angiopathies , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Male , PTEN Phosphohydrolase , Genetics , Metabolism , Panax , Chemistry , Phytotherapy , RNA, Messenger , Genetics , Metabolism , Rats , Rats, Inbred Strains , Rats, Wistar , Signal Transduction
10.
Article in Chinese | WPRIM | ID: wpr-356726

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mechanism of Shenqi compound recipe (SQCR) anti-earlier diabetic artherosclerosis in GK rats.</p><p><b>METHOD</b>Four-month specefic pathogen free (SPF) GK rats were divided randomly according to blood glucose level into four groups: model group (5 mL x kg(-1) x d(-1) sterile water), ramipril group (positive control, 1 mg x kg(-1) x d(-1)), SQCR low dosage (0.72 g x kg(-1) x d(-1)) and SQCR high dosage group (2.88 g x kg(-1) x d(-1)) and Wistar rats as normal control group(5 mL x kg(-1) x d(-1) sterile water). GK rats took high-fat diet freely and meanwile were injected N-omega-nitro-L-arginine methyl ester (L-N-AME) intra-peritoneally with the dose of 10 mg x kg(-1) x d(-1) in order to induce earlier diabetic artherosclerosis, while normal control group took regular diet and were injected normal saline intra-peritoneally. In the experiment periods, each group was administrated correspondent substance respectively for 32 d. At the end, sampling blood by abdominal aorta and picking aorta on ice. Determined monocyte chemoattractant protein-1 (MCP-1) concentration by ELISA, messenger ribonucleic acid (mRNA) expression of MCP-1 and peroxisome proliferator-activated receptor gamma (PPARgamma) in aorta by reverse transcriptase PCR (RT-PCR).</p><p><b>RESULT</b>Concentrations of MCP-1 in serum in SQCR low and high dosage groups and the mRNA expression of MCP-1 in SQCR high dosage group were all decreased significantly compared with model group (P < 0.05). The mRNA expression of PPARgamma in SQCR low and high dosage groups all increased compared with model group (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Inhibiting the mRNA and protein expression of MCP-1 and upregulating the mRNA expression of PPARgamma in aorta might be contribute to SQCR anti-earlier diabetic artherosclerosis in GK rats partly.</p>


Subject(s)
Animals , Aorta , Metabolism , Astragalus propinquus , Chemistry , Atherosclerosis , Metabolism , Chemokine CCL2 , Blood , Genetics , Diabetes Mellitus, Type 2 , Metabolism , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Male , PPAR gamma , Genetics , Panax , Chemistry , Plants, Medicinal , Chemistry , RNA, Messenger , Genetics , Random Allocation , Rats , Rats, Wistar
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