The Study Of Renoprotection By Rhaponticum Uniflorum On Diabetic Nephropathy

Objective: Diabetic nephropathy is a common complication of diabetic complications and a leading cause of end stage renal failure. Various mechanisms have been identified contributing development of diabetic nephropathy, such as heredity, hemodynamic factors, advanced glycation end products and many cell factors.Recently, a lot of researches have been done to intervene diabetic nephropathy by inhibiting VEGF, and demonstrated that extracellular signal regulated kinase (ERK) can regulate the expression of many kinds of cytokines, signal protein or growth factors, who plays a key role in the process of myofibroblast hyperplasia and deposition of collagen . Rhaponticum uniflorum (RU)`s root has been used as a traditional chinese medine . Studys find that Rhaponticum uniflorum has the function of improving cell immunity, anti-inflammatory anti-sclerosis, anti-hypoxia, anti-oxidation and anti-senile. In this study, rhaponticum uniflorum was preventively applied to diabetic rats,aiming to observe its effect on blood glucose, urinary albumin, renal weight/ body weight, VEGF and P-ERK expression. The mechanism of renoprotective effect of rhaponticum uniflorum on diabetic nephropathy related to VEGF and P-ERK was specially studied.Methods:the rats were randomly divided into normal rats (group NC), streptozotocin-induced diabetic rats (group DM), diabetic rats treated with rhaponticum uniflorum with 1g/kg dosage every day (group DQ1), diabetic rats treated with rhaponticum uniflorum with 2 g/kg dosage every day (group DQ2) and diabetic rats treated with Fosinopril with10 mg/kg dosage every day(group DF).8 weeks later Ualb was measured by immunoradioassay as glomerular injury index. Immunocytochemical technique and Westernblotting Were used to measure the expression of VEGF and phosphate (P-)ERK1/2 protein respective.pathological changes of renal tissue were observed under light microscopy and microscopy.Results:1.8 weeks later,the blood glucose levels of group DM ,DQ₁,DQ₂ and DF were higer than that of group NC (p<0.01), the blood glucose levels of group DM and DF was similar(P>0.05),but much higer than that of group DQ₁ and DQ₂ (P <0.01,0.05).kidney atrophy, creatinine and urinary albumin in group DQ₁,DQ₂,DF were lower than those in group DM(P〈0.05,0.01,0.01).The above-mentioned data in DQ₁,DQ₂,DF,DM were all higher than those in group NC(P〈0.01). Group DQ₂ was similar to what Fosinopril did. 2. Immunohistochemistry results show that In group NC VEGF staining in tubular, glomerulus are negative. while in group DQ₁,DQ₂,DF,DM showing VEGF staining in tubular and glomerulus.In group NC showing P-ERK staining in some cortical collecting ducts,glomeruli and other tubular segments are negative,while in group DQ₁,DQ₂,DF,DM showing P-ERK staining in tubular and glomerulus. 3.8 weeks later VEGF and P-ERK protein expression in group DQ₁,DQ₂ and DF were higer than that of group NC ,lower than that of group DM. 4.The results in both light microscopy and electron microscopy of renal tissues in pathological morphology showed that rhaponticum uniflorum could reduce renal hypertrophy, mesangial hyperplasia and inhibiting mesangial proliferation, as was similar to Fosinopril.Conclusion:1. Rhaponticum uniflorum has the function of lowing blood glucose level of diabetic rat. 2.Rhaponticum uniflorum can attenuates proteinuria,improproves renal pathology and protects against renal function. 3.the overexpression of P-ERK and VEGF may play an important role in the devolpment of DN. 4.VEGF is possible upstream of ERK MAPKS singnal transduction. 5.The mechanism of renoprotective effect of rhaponticum uniflorum possibly through down-regulating the expression of VEGF and P-ERK1/2.