| Abstract:Objective:To observe the effects of valsartan on diabetic nephropathy and its mechanism by valsartan intervention on diabetic nephropathy SD rats. To explore the effects of valsartan on HK-2cells tubular transdifferentiation induced by high glucose. Methods:(1)The DN rats model was established by injecting Streptozotocin(STZ), randomly divided into five group:CON group and DM group, valsartan(VT) group, GSH group, VT&GSH group. After continuous treatment for8weeks, detecting kidney pathological changes by HE staining; tseting the hemorheology on Abdominal aortic blood; measuring Ang II and VEGF by enzyme-linked immuno sorbent assay; testing COL-III by immunohistochemical staining.(2)The HK-2cell was randomly divided into Control group, high sugar group and valsartan group. Each group was set up to six holes, culture media and cell was collected after48h, testing HK2cell proliferation and toxicity by the way of CCK-8; detecting AP-1on immunohistochemical staining; measuring AP-1and Periostin mRNA by RT-PCR. Results:(1)①HE staining and Masson staining: Compared with normal group,renal tubule was significantly expanded wider, showing interstitial inflammatory cell infiltration, significant degree of renal interstitial fibrosis in the model group rats; Compared with the model group, valsartan group and Val&GSH group inflammatory cells and the level of renal interstitial fibrosis were obviously decreased, no significant fibrosis.②hanges in blood rheology:Compared with Control group, the index of Blood rheology was obviously increased in DN group (P<0.05). Compared with model group, valsartan group,GSH group and Val&GSH could improve the indexes of DN rat blood rheology (P<0.05).③ELISA:Compared with Control group, AngⅡ and VEGF were Significantly increased in DN group (P<0.05). Compared with model group, Ang Ⅱ and VEGF were Significantly decreased in valsartan group,GSH group and Val&GSH group(P<0.05).(2)KK-8:the cell proliferation activity is the best in high group;②mmunohistochemistry results:Compared with Control group,the express of COL-Ⅲ was Significantly increased in high sugar group(P<0.05).③The result of PT-PCR:Compared with Control group, the mRNA of AP-1and periostin was Significantly increased in high sugar group(P<0.05). Conclusion:(1) Valsartan could reduce the expression of VEGF, reduce urinary albumin, reduce oxidative damage, improve blood rheology by blocking the effect of angiotensin Ⅱ and reduce the streptozotocin-induced renal injury with rats DN, delay renal interstitial fibrosis. Valsartan combined with reduced glutathione its effect is better.(2) Valsartan could inhibited HK-2cells tubular transdifferentiation, reduce expression of AP-1and periostin in high glucose by blocking the effect of angiotensin Ⅱ. |
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