| [Background/Aims]The study is made up of two parts.In the first part,the authors summarized the pathogenesis and treatment of insulin resistance(IR)and interventional effects of Chinese herbal medicine(CHM).IR is one of the pathogenesis of many diseases occurred in the target-organs of insulin.The clinical diagnostic indicator of IR is the homeostasis model assessment insulin resistance index(HOMA-IR);The influence factors of IR include obesity,chronic microinflammation and lack of exercise;The relative signaling pathways contain insulin receptor substrate 1/phosphatidylinositol-3-kinase/serine threonine kinase(IRS1/PI3K/Akt)pathway,mitogen activated protein kinase(MAPK)pathway and Smad3 pathway.But not only that,IR also induces podocyte injury in diabetic nephropathy(DN).In addition,as a pathogenic factor of DN,it has been recognized as the potential pathogenesis during the progression of DN to end-stage renal disease(ESRD).In clinic,IR can be ameliorated by insulin sensitizer protecting against the kidney dysfunction.In addition to this,IR in some tissues or cells can be intervened in the different ways through the extracts of single CHM such as total flavones of Abelmoschus manihot(L.)medic(TFA),Astragalus polysaccharide,Berberine,Puerarin and Curcumin.In the second part,as the focus of this study,using the DN model rats,the authors tried to reveal roundly the effects and mechanisms of Huangkui capsule(HKC),a preparation of Chinese patent medicine,improving podocyte injury in vivo.[Methods)The DN rat models were established by the combinative methods,the high-fat diet,the unilateral nephrectomy and the intraperitoneal injection of streptozotocin(STZ).All rats were divided into 4 groups,the normal group,the vehicle group,the HKC group and the Rosiglitazone(ROS)group(8 rats for each group)according to the randomized controlled principle.The rats in each group were daily oral administrated with double distilled water(2 mL)or HKC suspension or ROS suspension respectively for 8 weeks.Urine of the rats was collected once every two weeks during the administration.After the drug administration for 8 weeks,all rats were anesthetized,and that their blood and the kidneys were collected respectively for detecting a series of parameters including the efficacy indexes,the podocyte injury related indicators and the IR related indicators.[Results]For these DN model rats,both HKC and ROS could improve body weight(BW),kidney appearance,kidney weight(KW),urine microalbumin/creatinine(UAlb/UCr),renal function and blood lipid;Neither HKC nor ROS could significantly affect blood glucose(BG);Both of them could improve the glomerular morphology,reduce the glomerular celluar population(GCP)and ameliorate extracellular matrix(ECM)accumulation and collagen deposition;HKC could improve the glomerular ultrastructure including foot process form and the thickness of glomerular basement membrane(GBM),whereas ROS had no the significant effects;Both of them could improve the expressions of nephrin and nephl in glomeruli and up-regulate the protein expressions of nephrin and nephl in the kidneys,however,the effects of HKC were better than ROS;Both of them could improve the fasting insulin(FIN)and HOMA-IR,but the effects of ROS were better than HKC;More importantly,both of them could improve the protein expressions of the key signaling molecules of IRS1/PI3K/Akt pathway in the kidneys in different extent,but the difference between HKC and ROS had no statistically significance.[Conclusions]By means of the DN model rats,the authors demonstrated ?The decrease in activation of IR and its signaling pathway induces podocyte injury,which is characterized by the down-regulation of nephrin and nephl protein expressions and foot process effacement;? HKC ameliorates podocyte injury and IR in vivo and its effects are different from ROS;?HKC protects against podocyte injury via regulating the activation of IRS1/PI3K/Akt signaling pathway and IR,which is similar to ROS;? HKC may be a natural insulin sensitizer. |
PDF Full Text Request