The Protective Effect And Mechanism Of Notoginseng Triterpenes On High Glucose Induced Injury In Glomerular Mesangial Cells And Rat’s Diabeitic Nephrophathy

Objective The aim of this research want to investigate the effects and mechanism of trifolium saponin extract--PPD-25-OH(PPD)on glomerular mesangial cells(GMCs)exposed to high glucose(HG)and rats of diabetic nephropathy(DNP),also observed the improving effects and relative mechanism on renal functions in vivo.Methods In the first section,GMCs were used and divided into 5 groups,included normal group,high glucose group,and different concentration PPD groups.The volume of GMCs,the total protein contents and survival rates of GMCs were observed.Enzyme-linked immunoabsorbent assay(ELISA)method was used to test the contents of interleukinin-6(IL-6)and tumor necrosis factor-α(TNF-α),stromal cell derived factor-1(SDF-1)and cyclooxygenase-2(COX-2).Moreover,the western blotting method was used to test the expression of serine threonine protein kinase(AKT)and p-AKT.In the second section,this study also used DNP model rats to observe the protective effects of different dosage of PPD-25-OH on renal functions,also observe the protein expression of monocyte chemotactic factor(MCP-1)and connective tissue growth factor(CTGF)by western blotting method to observe the relative mechanism.Results In vitro,HG group compared with NG group,the volume of GMCs and the total protein contents were increased,the survival rates of GMCs were decreased,the results showed significantly difference(P<0.05).Different concentration PPD groups compared with HG group,the volume of GMCs and the total protein contents were reduced and survival rates of GMCs were enhanced.Moreover,the contents of stromal cell derived factor-1(SDF-1),COX-2,IL-6 and TNF-α were also decreased by PPD-25-OH,these results showed significantly difference(P<0.05).Moreover,the Western blot method was used to test the expression of AKT and p-AKT,Western blot results showed,compared with normal control group,the content of AKT were increased in HG and PPD group,however,the expression of AKT were reduced in PPD group,compare with HG group,have the significantly difference(P<0.05).In vivo,different dosage of PPD-25-OH could reduce the levels of blood glucose,urine protein,urea nitrogen(BUN)and creatinine(Cr),(P<0.05).Different dosage of PPD-25-OH could improve the renal function,also reduced the expression of MCP-1and CTGF in renal tissue,compare with DNP group,have the significantly difference(P<0.05).Conclusions 1.Different concentration of PPD-25-OH could reduce volume and the total protein contents in GMCs,enhance survival rates to protect from the DNP injury.2.Different concentration of PPD-25-OH could reduce the contents of IL-6,TNF-α,SDF-1 and COX-2,the possible mechanism might through inhibited inflammatory factors via p-AKT-AKT signal pathway.3.Different dosage of PPD-25-OH could reduce the contents of BUN,Cr,and glucose,improve the renal functions and inhibit the hypertrophy in DNP rats.4.Different dosage of PPD-25-OH could reduce the expression of MCP-1and CTGF in DNP rats.