Effect of Yiqi Huayu Decoction Combined with Calcium Dobesilate in Treating Diabetic Kidney Disease with Qi Deficiency and Blood Stasis Syndrome and Its Effect on the Expression Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor 1 / 广州中医药大学学报

Objective To investigate the clinical efficacy of Yiqi Huayu Decoction(mainly composed of Astragali Radix,Dioscoreae Rhizoma,Poria,fried Euryales Semen,Ecliptae Herba,Rosae Laevigatae Fructus,charred Crataegi Fructus,Ligustri Lucidi Fructus,Salviae Miltiorrhizae Radix et Rhizoma,and Leonuri Herba)combined with Calcium Dobesilate in the treatment of diabetic nephropathy(DN)with qi deficiency and blood stasis syndrome,and to observe the effect of the therapy on vascular endothelial growth factor(VEGF)and insulin-like growth factor 1(IGF-1).Methods Ninety patients with DN of qi deficiency and blood stasis type were randomly divided into an observation group and a control group,with 45 patients in each group.All patients received basic hypoglycemic therapy and treatment for controlling blood pressure and regulating lipid metabolism disorders.Moreover,the patients in the control group were given Calcium Dobesilate orally,and the patients in the observation group were given Yiqi Huayu Decoction combined with Calcium Dobesilate.The course of treatment lasted for 3 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters and serum VEGF and IGF-1 levels in the two groups of patients were observed before and after the treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 3 months of treatment,the total effective rate of the observation group was 91.11%(41/45),and that of the control group was 75.56%(34/45).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After one month and 3 months of treatment,the TCM syndrome scores of both groups were significantly lower than those before treatment(P＜0.05),and the scores after 3 months of treatment in the two groups were significantly lower than those after one month of treatment(P＜0.05).The intergroup comparison showed that the reduction of TCM syndrome scores of the observation group was significantly superior to that of the control group after one month and 3 months of treatment(P＜0.01).(3)After treatment,the levels of renal function parameters such as serum creatinine(Scr),blood urea nitrogen(BUN),and glomerular filtration rate(GFR)in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the observation group's effect on the improvement of all renal function parameters was significantly superior to that of the control group(P＜0.01).(4)After treatment,the serum VEGF and IGF-1 levels in the two groups of patients were significantly lower than those before treatment(P＜0.05),and the observation group's effect on the decrease of serum VEGF and IGF-1 levels was significantly superior to that of the control group(P＜0.01).(5)In the course of treatment,no significant adverse reactions occurred in the two groups of patients,with a high degree of safety.Conclusion Yiqi Huayu Decoction combined with Calcium Dobesilate exerts certain therapeutic effect in treating DN patients with qi deficiency and blood stasis syndrome.The combined therapy can effectively down-regulate the serum levels of VEGF and IGF-1,significantly improve the renal function,and alleviate the clinical symptoms of the patients,with a high degree of safety.

Effect of neferine on diabetic nephropathy by regulating SDF-1/CXCR4 signal pathway / 上海交通大学学报（医学版）

Objective·To investigate the effect of neferine(Nef)on renal tissues of diabetic nephropathy(DN)rats and its related mechanism.Methods·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin,and the successfully constructed rats were randomly divided into DN group,Nef(low,medium and high)dose groups and Nef high-dose+pathway antagonist(AMD3100)group,with 10 rats in each group.At the same time,10 common rats were selected as the normal group.The levels of fasting blood glucose(FBG),24 h urinary protein,serum glycosylated hemoglobin(HbA1c),serum creatinine(Scr),blood urea nitrogen(BUN)and renal index of rats in the six groups were measured.Hematoxylin-eosin(H-E)and Masson staining were used to observe the pathological changes of renal tissues.The content of malondialdehyde(MDA)in renal tissues was determined by thiobarbituric acid(TBA)method,and the activities of superoxide dismutase(SOD)and catalase(CAT)in renal tissues were determined by water soluble tetrazolium(WST-1)method and ammonium molybdate method,respectively.The mRNA and protein expressions of stromal cell-derived factor-1(SDF-1)and CXC chemokine receptor 4(CXCR4)in renal tissues were detected by quantitative real-time PCR(qPCR)and Western blotting,respectively.Rat renal tubular epithelium cells NRK-52E were induced by high glucose(30 mmol/L glucose)to establish DN cell model.The cells were divided into control group,high glucose(HG)group,HG+Nef(low,medium and high)dose(i.e.HG+Nef-L,M and H)group,and HG+Nef-H +AMD3100 group.SOD and CAT activities were detected by WST-1 method and ammonium molybdate method,respectively.MDA content was detected by TBA method.The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting,respectively.CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate,respecti-vely.Results·Compared with the DN group,the levels of FBG,24 h urinary protein,HbA1c,Scr,BUN,renal index and MDA content in Nef(low,medium and high)dose groups and Nef high-dose+AMD3100 group were decreased,the mRNA and protein expressions of SDF-1 and CXCR4 were increased,and the activities of SOD and CAT were increased(all P<0.05).The degree of pathological damage and fibrosis of renal tissues was reduced;all of the above changes were dose-dependent.AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats.Compared with the HG group,NRK-52E cell viability,SOD and CAT activities,and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L,M and H groups,while apoptosis rate and MDA content were decreased(all P<0.05).AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage.Conclusion·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway,playing a renal protective role.

Expression of platelet microparticles in patients with diabetic nephropathy and its relationship with renal damage / 中国输血杂志

【Objective】 To investigate the expression levels of platelet microparticles(PMPs) in patients with diabetic nephropathy (DN) and their relationship with renal injury. 【Methods】 Thirty DN patients, 30 T2DM patients without DN and 30 healthy controls were enrolled. Flow cytometry was used to detect the quantity and phenotype of PMPs, and ELISA was used to measure the levels of plasma renin, angiotensin Ⅱ (angiotoninⅡ, AngⅡ), vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and transforming growth factor-β1(transforming growth factor-β1, TGF-β1). Kidney function was determined by blood biochemistry. 【Results】 The quantity of PMPs in the DN group was (1 564±346) particles/μL, which was significantly higher than that in the non-DN group (1 246±312) particles/μL and the control group (1 223±299) particles/μL (P<0.05). The PMPs in the DN group mainly expressed CD62P and CD41a, accounting for (76.5±12.3)%. Moreover, the levels and activation of PMPs increased with the progression of DN. The quantity of PMPs was positively correlated with renin and other factors (r=0.56-0.62, P<0.05), negatively correlated with the glomerular filtration rate (GFR) (r=-0.64, P<0.05), and positively correlated with the urinary albumin excretion rate (UAE) (r=0.66, P<0.05). PMPs were also an independent influencing factor of UAE (β=12.34, P<0.05). 【Conclusion】 PMPs expression is elevated in DN patients, which may be associated with renal injury, but it is insufficient to confirm its role in the pathogenesis of DN.

Hypomagnesemia � An overlooked parameter in type 2 diabetes mellitus

Background: Diabetes Mellitus refers to a group of common metabolic disorders that share the phenotype of Hyperglycemia. It is the leading cause of morbidity and mortality throughout the world with an estimated worldwide prevalence of 439 million by 2030 and 19% of world抯 DM patients are Indians. Magnesium is an important co-factor for various enzymes involved in Insulin secretion and is involved in sodium-potassium ATPase pump. 25%-38% of Type 2 DM patients had Hypomagnesemia, which has also contributed in developing microvascular complications such as Diabetic Retinopathy (DR) and Diabetic Nephropathy (DN). Various studies have suggested that Magnesium supplementation in Type 2 DM patients with Hypomagnesemia have shown beneficial effects on insulin sensitivity and glucose metabolism. Aim and objectives: To study the prevalence of Hypomagnesemia in Type 2 DM patients and to study the association of Hypomagnesemia with microvascular complications such as DR and DN. Materials and methods: It is a hospital based Observational study carried out in 2022 for a period of 1 year including 60 patients fulfilling the ADA criteria for diagnosing T2DM and patients with Diabetic Retinopathy and Diabetic Nephropathy, and excluding patients with Malabsorption, Chronic diarrhoea, Renal Failure on diuretic therapy, Sepsis, Pancreatitis. Serum Magnesium levels of 1.6 mg/dl � 2.6 mg/dl is considered as normal range. Serum Magnesium were measured using Xylidyl blue colorimetric method. Results: The Mean age of the patients in our study was 55.89 years. Among 60 patients diagnosed with Diabetes Mellitus, 42 patients had Hypomagnesemia, 18 patients had Normomagnesemia (p- value: <0.0001). Patients with an HbA1c levels > 7% had Hypomagnesemia when to compared to patients with HbA1c <7% with a significant p value of 0.009. Hypomagnesemia was also associated with Diabetic Retinopathy and Diabetic Nephropathy with a significant p-value of 0.013 and 0.009 respectively. Conclusion: In our study, it has shown that patients with uncontrolled T2DM had Hypomagnesemia, which is also associated with micro-vascular complications of T2DM such as DR and DN.

Effects of Intestinal Flora and Local Renin-angiotensin System on Diabetic Nephropathy and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is a common clinical complication of diabetes， the main cause of end-stage renal disease （ESRD）， and a key determinant of survival in diabetic patients. The pathogenesis of DN is complex， and it is currently believed to be associated with hemodynamic abnormalities， intestinal flora disturbances， glucose and lipid metabolism disorders， oxidative stress， genetic susceptibility， and protein non-enzymatic glycosylation. The local renin-angiotensin system （RAS） has always been the core of the pathogenic and progressive changes of DN. Once activated， it will induce the massive release of oxygen free radicals in the blood vessels， damage the endothelial function， and affect the microcirculation of the body. The recent studies demonstrate that intestinal flora and its metabolites may affect the occurrence and development of DN by activating or antagonizing the local RAS. Compared with western medicine treatment， traditional Chinese medicine （TCM） has the advantages of multiple targets and little toxic and side effects. Many TCM scholars have found that single herbs， their active ingredient extracts， and TCM compound prescriptions can improve kidney function by regulating the local RAS or intestinal flora. Specifically， the Chinese medicinal materials tonifying spleen （Codonopsis Radix， Dioscoreae Rhizoma， Atractylodis Macrocephalae Rhizoma， and Poria）， replenishing kidney （Rehmanniae Radix Praeparata， Corni Fructus， and Pseudostellariae Radix）， and activating blood， resolving stasis， and dredging collaterals （Hirudo， Salviae Miltiorrhizae Radix et Rhizoma， and Angelicae Sinensis Radix） have the regulatory effect. This article summarizes the roles of intestinal flora and local RAS in the occurrence and development of DN， and analyzes the animal experiments or clinical trials of TCM intervention in DN in recent years， aiming to provide more therapies and a theoretical basis for the treatment of DN with integrated TCM and Western medicine.

Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro / 中国天然药物

Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.

PK2/PKR1 signaling pathway participates in geniposide protection against diabetic nephropathy in mice / 中国中药杂志

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.

Effect of Zishenwan on Pyroptosis and Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells in Diabetic Nephropathy Mice / 中国实验方剂学杂志

Objective:To study the efficacy and mechanism of Zishenwan （ZSW） against pyroptosis and epithelial-mesenchymal transition （EMT） of renal tubular epithelial cells in diabetic nephropathy （DN） mice， so as to provide evidence for the treatment of DN with ZSW. Method:The <italic>db/db</italic> mice with spontaneous diabetes were randomly divided into the model group， dapagliflozin （1.0 mg·kg^-1） group， and high-， medium-， and low-dose （6.0， 3.0， 1.5 g·kg^-1） ZSW groups. The non-diabetic <italic>db/m</italic> mice were classified into the normal group. The ones in the model and normal groups were given an equal volume of deionized water by gavage， while those in the other groups were intervened with the corresponding drugs for 12 weeks. The fasting blood glucose （FBG） level was tested at tail vein once every two weeks. The levels of urine albumin-creatinine ratio （ACR）， <italic>β</italic>-N-acetyl-D-glucosaminidase （NAG）， and cystatin C （CysC） were detected once every four weeks. After 12 weeks of administration， the blood sampled from eyeballs was used for measuring the blood urea nitrogen （BUN） and serum creatinine （SCr）. The pathological changes in renal tissues were observed by light microscopy and transmission electron microscopy. The expression of EMT markers in the renal tubular epithelium was analyzed by immunohistochemistry （IHC）. The in situ terminal end-labeling （TUNEL） staining was conducted to analyze the nuclear damage of renal tubular epithelial cells. The protein and mRNA expression levels of EMT markers， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasome and pyroptosis-related inflammatory cytokines in renal tissues were separately assayed by Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Result:Compared with the normal group， the model group displayed significantly increased FBG， BUN， serum SCr， ACR， NAG， and CysC （<italic>P</italic><0.01）， impaired renal tissues， altered EMT marker expression intensities and levels （<italic>P</italic><0.01）， and elevated TUNEL-positive rate and protein and mRNA expression levels of pyroptosis-related inflammatory cytokines and NLRP3 inflammasome （<italic>P</italic><0.01）. Compared with the model group， ZSW and dapagliflozin significantly decreased the levels of FBG， BUN， serum SCr， ACR， NAG， and CysC （<italic>P</italic><0.01）， relieved the pathological injuries in renal tissues， changed the EMT marker expression intensities （<italic>P</italic><0.01） and protein and mRNA expression levels （<italic>P</italic><0.05， <italic>P</italic><0.01）， and down-regulated the TUNEL-positive rate （<italic>P</italic><0.01） of renal tubular epithelial cells as well as the protein and mRNA expression levels of pyroptosis-related inflammatory cytokines （<italic>P</italic><0.01） and NLRP3 inflammasome （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:ZSW alleviates DN possibly by inhibiting pyroptosis and EMT in renal tubular epithelial cells.

Yiqiyangyin Huoxuetongluo Prescription Reduces Renal Cell Apoptosis in Rats with Diabetic Nephropathy by Inhibiting JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Yiqiyangyin Huoxuetongluo prescription on janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway and cell apoptosis in rats with diabetic nephropathy （DN）， and to explore the mechanism of its intervention in DN. Method:A total of 100 SD rats were randomly divided into an experimental group （<italic>n</italic>=80） and a normal group （<italic>n</italic>=20）. The DN model was induced by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） in the experimental group， and confirmed by the pathological changes of kidney tissues in rats （three in each group） observed under light and electron microscopes. The model rats were randomly divided into a model group （normal saline， equal volume）， low-， medium-， and high-dose （5.775， 11.550， and 23.100 g·kg^-1） Yiqiyangyin Huoxuetongluo prescription groups， and an irbesartan group （irbesartan tablets， 0.016 g·kg^-1）. After drug intervention （<italic>i.g</italic>.， once a day for 16 consecutive weeks）， the 24-hour urine total protein （UTP）， serum total cholesterol （TC）， triglyceride （TG）， creatinine （SCr）， and blood urea nitrogen （BUN） levels of the rats were measured. Western blot was used to detect the protein expression of JAK2/STAT3 signaling pathway. Immunohistochemistry was used to determine the protein expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， zonula occludens-1 （ZO-1）， and actinin-4 in rat kidney tissues. Result:Compared with the normal group， the model group exhibited elevated UTP， serum TC， TG， BUN， and SCr levels （<italic>P</italic><0.05）， severe pathological damage of rat kidney tissues， up-regulated expression of phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3）， and Bax， increased renal cell apoptosis， and diminished expression of Bcl-2， ZO-1， and actinin-4 （<italic>P</italic><0.05）. Compared with the model group， the Yiqiyangyin Huoxuetongluo prescription group and the irbesartan group showed dwindled UTP， serum TC， TG， BUN， and SCr levels （<italic>P</italic><0.05）， relieved pathological damage of rat kidney tissues， down-regulated p-JAK2， p-STAT3， and Bax expression， and up-regulated expression of Bcl-2， ZO-1， and actinin-4 （<italic>P</italic><0.05）. Conclusion:Yiqiyangyin Huoxuetongluo prescription can reduce renal cell apoptosis and improve the prognosis of DN by inhibiting the activation of JAK2/STAT3 signaling pathway.

Treatment of Diabetic Nephropathy Based on Theory of Generation and Restriction Among Five Elements / 中国实验方剂学杂志

The theory of generation and restriction among five elements， as one of the basic theories in traditional Chinese medicine （TCM）， reveals that treating disease should focus on the root. Since its first record in Huangdi's Internal Classic （Huang Di Nei Jing）， this theory has been covered in many chapters of Synopsis of the Golden Chamber （Jin Gui Yao Lue） and further developed by physicians of later generations， allowing it to serve as a guide for clinical treatment of various diseases. Diabetic nephropathy （DN） is one of the most common complications of diabetes and also a main risk factor for death and disability by virtue of the long-term disease course and complex symptoms. At present， no specific drug is available in western medicine. Considering the close relationship of its complicated etiology and pathogenesis with the five zang organs， DN treatment should focus not only on the kidney， but also other zang organs. Guided by the theory of generation and restriction among five elements， this article believes that DN mainly results from kidney deficiency combined with spleen deficiency and its dysfunction in regulating the water passage. In addition， the exuberance of heart fire and the failure of liver to govern the free flow of Qi are also responsible for the occurrence of DN. Clinically， the therapeutic methods proposed based on theory of generation and restriction among five elements are recommended for DN treatment after the differentiation of actual manifestations into specific syndromes. Specifically， the method of replenishing Huo to nourish Tu is applicable to DN patients with spleen and kidney yang deficiency， the method of nourishing Shui to moisten Mu to those with liver and kidney yin deficiency， the method of mutual generation between Jin and Shui to those with lung and kidney yin deficiency， the method of banking up Tu to generate Jin to those with lung and spleen Qi deficiency， the method of purging the heart and tonifying the kidney to those with non-interaction between heart and kidney， and the method of banking up Tu to control Shui to those with spleen deficiency and fluid retention. Such timely and effective interventions are conducive to delaying the development of DN to end-stage renal disease （ESRD） and improving the clinical outcomes. This article discusses the application of the theory of generation and restriction among five elements in TCM to DN treatment， aiming to provide a theoretical basis for the future application of such new diagnosis and treatment ideas.

Study on the Relationship between Serum Omentin-1 Level and Degree of Kidney Injuryin Patient with Type 2 Diabetic Nephropathy / 现代检验医学杂志

Objective To explore the relationship between serum Omentin-1 level and degree of kidney in juryin patient with type 2 diabetic nephropathy.Methods 100 diabetic patients with suspected DN were devided into two groups:DM (44 cases) and DN (56 cases) group,and by Mogenson,DN group were devided into DN1 (30 cases) and DN2 (26 cases).In addition 80 healthy subjects were selected as control group.HbA1c,BUN,Scr,β2-MG,HOMA-IR and serum Omentin-1 leves were detected by the standard method.Results There were obvious differences of HbA1c,BUN,Scr,β2-MG,HOMA-IR and Serum Omentin-1 levels among DN,DM and NC (F=6.078～16.231,all P＜0.05).Apart of HbA1c and HOMA-IR,others were no differences between DM group and NC group (t=1.421～2.637,all P＞0.05).There were significant differences of these indicators between DN and NC group (t=8.981～26.785,all P＜0.05).DN group was higher significantly than these in DM group (t=6.371～21.673,all P＜0.05),and HbA1c,BUN,Scr and β2-MG levels had no statistical difference between DN1 and DN2 group (t 0.981～1.389,all P＞0.05).HOMA-IR level in DN2 was higher than that in DN1 group,and serum Omentin 1 declined (t=68.451～76.814,all P＜0.01).There were negative correlation between HOMA IR and serum Omentin-1 leves (r=-0.405,P＜0.05).Conclusion Serum Omentin-1 was related to insulin resistance.Serum Omentin 1 in serum may be a role indicator for impairment of renal function for diagnosis of type 2 diabetic nephropathy.

Preliminary study of the dose-proportion relation of Tibetan medicine Siwei Jianghuang Prescription on diabetic nephropathy rats induced by STZ / 中成药

AIM To investigate the dose-proportion relation of Tibetan medicine Siwei Jianghuang Prescription (SJP) for protective effects on diabetic nephropathy (DN),and the underlying mechanism.METHODS Diabetes mellitus rats induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) were randomly divided into model group,metformin support group,and eight SJP groups with dose-proportion variation (with reference to the uniform design method) for corresponding drug administration once a day,for four weeks.Measurement of fasting blood glucose (FBG) by a blood glucose meter,the concentrations of blood urea nitrogen (BUN),uric acid (UA),serum creatinine (SCr) and total protein (TP) by chemical methods,serum transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) by ELISA kits were conducted,the pathological morphology observation and glomerular basement membrane thickness detection by electron microscope were accomplished as well.Principal components analysis (PCA) and multivariate progressive regression analysis (MSRA) were employed to analyze the relationship between the dose-proportion to pharmacodynamics.RESULTS The resultant indexes revealed variant pharmacological improvement in each treatment group.MSRA results showed that the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr,and UA had correlative relations with a multiple linear or a multiple non-linear in all groups,which regression equation had a statistical significance (P ＜ 0.05);TGF-β1 level and total protein index with the dose-proportion had no linear or non-linear relation,which the regression equation statistical showed non-significance (P ＞ 0.05).In the global optimization comparison around the range of uniform design,the optimal dosage of the rats model was Curcumae Longae Rhizoma ∶ Berberidis dictyophyllae Cortex ∶ Phyllanthi Fructus ∶ Tribuli Fructus =1 ∶ 2 ∶ 1 ∶ 2.CONCLUSION Siwei Jianghuang Prescription shows better therapeutic effects on DN,which may be related to reducing the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr and UA.

Autoimmune in diabetes mellitus and diabetic nephropathy / 中国糖尿病杂志

Diabetes mellitus (DM ) was the third largest chronic disease in the world and the number of patients in China ranked first. Diabetic nephropathy (DN ) as one of the most serious complications of DM was the main cause of death in DM patients along with the incidence of DM gradually increasing. The complex pathogenic mechanism of DN was composed of many factors such as the disorder of glucose metabolism ,inflammation and immune response. Under the special environment of the DM , autoimmunity was an important factor for the occurrence and development of DN. Immune cells ,cytokines and autoantibodies influenced each other resulting in impairment of renal function and affected the progression of DN. Further research on the immune related factors in DN and DM has important value for the prevention and treatment of these diseases.

Exosomes:their extraction and its research progress in the diagnosis and treatment of diabetic nephropathy / 国际药学研究杂志

Exosomes are membrane vesicles secreted by various cells containing unique proteins and miRNA from secretory cells.They can reflect the physiological and pathological state of secretory cells,and play an important role in cell-to-cell communica?tion.In recent years,the exosomes have become the focus of research,which brings hope for diseases that can not be treated effective?ly.This review aims to summarize the extraction methods,biological markers of diabetic nephropathy(DN)and the potential of exo?somes as drug carriers,hoping to bring new ideas for future studies on the occurrence and development mechanisms as well as the treat?ment of DN.

Protective effects and mechanism of glycosides/phenol component of Moutan Cortex on renal injury of diabetic nephropathy rats / 中国中药杂志

To evaluate the protective effects of glycosides/phenol component of Moutan Cortex (MC) on renal injury of diabetic nephropathy (DN) rats based on renal function parameters and histopathological examinations(HE staining and transmission electron microscope),and explore its possible mechanism by establishing DN rat models induced by high-sugar high-fat diet combined with streptozotocin (STZ). The results showed that compared with the model group, the MC glycosides/phenol component high and low dose groups(0.808, 0.404 g•kg⁻¹•d⁻¹) could significantly improve serum creatinine, blood urea nitrogen, urine protein and other abnormal renal function parameters. HE staining and transmission electron microscope results showed thickening of glomerular basement membrane, proliferation of mesangial cells and damages of podocyte structure in major rats of model group. However, the intervention of glycosides/phenol component of MC could effectively protect the glomerular injury. To explore its possible mechanism, the expressions of TGF-β1, fibronectin (FN) and collagen Ⅳ in renal tissues of rats in each group were detected by Western blot and immunohistochemical assay, and the phosphorylation levels of downstream effect factors (Smad2/3, p38MARK) of TGF-β1 were detected. The results showed that glycosides/phenol component of MC could effectively antagonize the activity of TGF-β1, lower the expressions of fibronectin (FN) and collagen Ⅳ inextracellular matrix (ECM), and resist against the thickening of glomerular basement membrane. More importantly, its protective effect on renal injury in DN rats may be associated with interfering the conduction of Smad, MARK pathways and resisting against the TGF-β1-induced ECM accumulation.

Research progress of the effect of epithelial-mesenchymal transition on diabetic renal interstitial fibrosis / 中国糖尿病杂志

[Summary] The epithelial‐mesenchymal transition (EMT) is a biological process in which epithelial cells are converted into cells with mesenchymal phenotype in specified physiological and pathological conditions. EM T plays a critical role in proper embryonic development ,tissue regeneration ,cancer metastasis and organ fibrosis. EM T can be divided into three subtypes (Ⅰ ,II and Ⅲ ) based on different biological context ,of which type II EMT contribute importantly to the development of organ fibrosis.Renal interstitial fibrosis (RIF) is an important pathological feature of diabetic nephropathy (DN). The understanding of molecular mechanisms of this process tubular EM T may provide a clue to intervene the development of DN through suppressing EM T and reversing RIF.

Role of endothelial cell injury in the pathogenesis of diabetic nephropathy / 中国糖尿病杂志

[Summary] Diabetic nephropathy is one of the major chronic microvascular complications of diabetes ,which is the leading cause of end‐stage renal disease ,as well as the main cause of death in diabetic patients. Glomerular endothelial cell is an important component of the glomerular filtration barrier ,which is directly related to the materials of circulation ,and it can be easily damaged by glucose ,lipid and inflammatory factors. Under the hyperglycemia ,the PKC pathway ,the polyol pathway and oxidative stress were activated ,producing an excess of advanced glycation end products and reactive oxygen species ,which damage the endothelial nitric oxide synthase ,reduce the generation of nitric oxide ,while produce a large number of Ang Ⅱ. Ang Ⅱ damage the endothelial cell. In addition ,there are crosstalk between glomerular endothelial cells and endothelial cells ,which also cause endothelial cell injury. Here ,we reviewed the role of endothelial cell injury in the pathogenesis of diabetic nephropathy.

Study on the Significance of Detecting MMP-1 0 Level in Patients with Type 2 Diabetic Nephropathy / 现代检验医学杂志

Objective To explore the significance of detecting serum MMP-10 in type 2 diabetic nephropathy.Methods 100 diabetic patients with suspected DN were devided into two groups,that was DM(42 cases)and DN(58 cases)group,and 60 casescontrolgroup(NC).By Mogenson,DN1(30 cases)and DN2(28 cases),HbA1c,BUN,Scr,UAER,β2-MG and MMP-10 leves were detected by the standard method.Results There were obvious differences of HbA1c,BUN,Scr,UAER,β2-MG and MMP-10 levels among DN,DM and NC(P0.05).DN group was higher significantly than these in DM group(P<0.05),and HbA1c,BUN,Scr,UAER, andβ2-MG levels had no statistical difference between DN1 and DN2 group.MMP-10 level in DN2 was higher than that in DN1 group(P<0.05).Conclusion MMP-10 in serum may be a role indicator for impairment of renal function for diagnosis of type 2 diabetic nephropathy.

Significance of Combined Detection of Serum Retinol-Binding Protein and AnnexinA2 in Diabetic Nephropathy / 现代检验医学杂志

Objective To explore the significance of detection serum Retinol-Binding Protein and AnnexinA2 in diabetic ne-phropathy.Methods According to 24-UAER level,80 diabetic patients with suspected DN were devided into three groups, that was A (25 cases),B (26 cases)and C (29 cases)group,and control group (NC)was 25 cases.HbA1c,BUN,Scr,UA and RBP leves were detected by the standard method.The expression level of Annexin A2 were detected by real-time PCR. Results There were obvious differences of HbA1c,BUN,Scr,UA and RBP levels among three groups and NC group (t=4.64~13.65,P0.05),there were differences of RBP (t=15.26,P<0.05).To HbA1c,BUN,Scr UA and RBP,there were differences be-tween A groups and C groups (t=5.26~25.33,P<0.05),there were the same results between B groups and C groups (t=4.02~18.33,P<0.05).To expression level of AnnexinA2 there were differences among three group and NC group ((t=13.45~24.25,P<0.05)).There exist positive correlation between the expression of AnnexinA2 and RBP level (r=0.95, P<0.01).Conclusion Combined detection of serum RBP and expression level of AnnexinA2 may be a sensitive and early phase indicator for impairment of renal function for diagnosis of diabetic nephropathy.

Research progress on the role of transcription factor Nrf 2 in diabetic nephropathy / 中国糖尿病杂志

Oxidative stress and inflammation are two main factors in the progress of diabetic nephropathy(DN) and its complications. NF‐E2 p45‐related factor (Nrf2) is a crucial transcriptional factor which manipulates downstream genes that encode some antioxidant enzymes and phase Ⅱ detoxifying enzymes ,to maintain the redox homeostasis and cellular detoxification response. Therefore ,more and more researchers are focusing on the role of Nrf2 in DN. In this review ,the detailed role of Nrf2 in DN will be discussed. Hopefully ,our work can epitomize recent research progress and provide novel clues for diabetic nephropathy prevention and treatment.