Effects Of Puerarin Combined With Gliclazide On Renal Fibrosis And Its Mechanisms In Type2Diabetic Rats

Objective: To observe the effects of puerarin combined with gliclazide on renal fibrosisand to explore its possible mechanisms through testing the contents of Ang II and theexpression of MCP-1and TGF-β1mRNA and protein in kidneys of type2diabetic rats.Methods:64Wistar rats were used, of which8rats were randomly chosen for controlgroup, and the remaining rats were for making type2diabetic rats model by high-sugarhigh-fat food plus35mg·kg-1streptozotocin(STZ). The rats met for the criterion wererandomly divided into6groups: model group, gliclazide group(10mg·kg-1·d-1), puerarinlow-, middle-and high-dose groups(40,80,160mg·kg-1·d-1) and puerarin combined withgliclazide group(40mg·kg-1·d-1+5mg·kg-1·d-1). The drugs were given for6weeks. Then,the rats were anesthetized, abdominal aortic blood, kidneys were taken. Kidney tissureswere stained by HE and Masson staining. Serum creatinine (Scr) and blood ureanitrogen (BUN) were testted by automatic biochemical analyzer. Ang II contents,mRNA and protein expression of MCP-1and TGF-β1in kidney were detected byradioimmunoassay, Quantitative real time reverses transcription-PCR, and Western blot,respectively.Result:①Compared with the normal group, the body weight of rats in model groupdecreased significantly(P＜0.01); compared with the model group, the body weight ofrats in each treatment group reduced, especially in the puerarin combined withgliclazide group(P＜0.01).②Compared with the normal group, levels of blood glucose,Scr and BUN were significantly elevated; compared with the model group, all treatments decreased Scr and BUN in blood, of which pueraria with gliclazide showedmore obvious(P＜0.01).③Compared with normal group, AngⅡ contents, mRNA andprotein expression of TGF-β1and MCP-1significantly increased; compared with modelgroup, all treatments reduced levels of renal Ang Ⅱ(P＜0.01or P＜0.05); and alltreatments except for low-dose puerarin inhibited mRNA and protein expression ofTGF-β1and MCP-1, with the combination therapy showing mark effect(P＜0.01).④Compared with normal group, glomerular renal capsule narrowed, mesangial matrixincreased; compared with model group, all treatments improved the pathologicalinjuries to varying degrees,, with pueraria in combination with gliclazide showing besteffect(P＜0.01).Conclusion: Puerarin combined with gliclazide significantly improves renal fibrosisand collagen deposition in diabetic rats, and its mechanisms may be related to loweringblood glucose, reducing content of Ang Ⅱ, inhibiting mRNA and protein expression ofTGF-β1and MCP-1in kidney.