【摘要】 目的:研究葡萄籽原花青素(GSP)对糖尿病大鼠肾保护作用的分子生物学机制,为GSP治疗糖尿病肾病提供实验依据。方法:雄性Wistar大鼠尾静脉注射0.1%链脲佐菌素(STZ)建立糖尿病大鼠模型,成模后随机分为糖尿病组(DM组)和糖尿病GSP治疗组(GSP组,GSP 250 mg.kg-1.d-1),另设正常对照组(C组)。观察24周后测量大鼠体重、收缩压、肾重/体重和24 h尿蛋白定量;采血测定空腹血糖(FPG)、尿素氮(BUN)、肌酐(SCr)和糖基化血红蛋白(HbA1c);观察糖尿病大鼠肾脏病理改变,并应用Western blotting和免疫组化法测定肾组织谷胱甘肽S-转移酶μ亚型(GSTM)和核因子E2相关因子2(Nrf2)的表达。结果:实验开始时3组大鼠体重无明显差异(P>0.05),24周时DM组大鼠较C组大鼠体重显著下降(P<0.01),治疗后GSP组大鼠体重较DM组增加,但无显著差异(P>0.05)。第24周时DM组大鼠与C组相比较,收缩压、FPG、HbA1c、肾重/体重、24 h尿蛋白定量、BUN和SCr水平显著升高(P<0.01)。治疗后GSP组大鼠与DM组比较FPG和HbA1c水平降低,但无显著差异(P>0.05),收缩压、24 h尿蛋白定量和肾重/体重显著降低,(P<0.01),BUN和SCr水平显著降低(P<0.05)。GSP组肾组织病理改变较DM组改善。GSTM和Nrf2表达在DM组表达较C组上调,在GSP组治疗后回调(P<0.05)。结论:GSP可能通过Nrf2下调GSTM表达而起肾保护作用。更多还原

【Abstract】 AIM: To investigate the potential mechanisms of renoprotective effect of grape seed proanthocyanidin(GSP) on diabetic nephropathy.METHODS: Male Wistar rats were injected with 1% streptozotocin(STZ) intravenously to induce diabetes mellitus(DM).The diabetic rats were randomly divided into 2 groups: diabetes group(DM group) and GSP treatment group(GSP group,GSP 250 mg·kg-1·d-1).The normal Wistar rats served as control(C group).Body weight(BW),systolic pressure,kidney weight/body weight(KW/BW),fasting plasma glucose(FPG),blood urea nitrogen(BUN),serum creatinine(SCr),glycosylated hemoglobin(HbA1c) and 24 h urine protein were determined 24 weeks after STZ intervention.The pathological changes of the renal tissues were observed.The protein levels of glutathione S-transferase mu(GSTM) and nuclear factor-erythroid 2-related factor 2(Nrf2) in the renal tissues were determined by Western blotting and immunohistochemistry.RESULTS: Compared with C group,BW in diabetic rats decreased(P<0.01).The levels of systolic pressure,FPG,HbA1c,KW/BW,24 h urine protein,BUN and SCr in DM group were higher than those in C group(P<0.01).After treated with GSP,the levels of systolic pressure,KW/BW,24 h urine protein,BUN and SCr in DM rats were lower than those in DM rats without treatment(P<0.01 or P<0.05).The pathological changes were ameliorated in GSP group.The expression of GSTM and Nrf2 was up-regulated in the kidneys of diabetic rats and down-regulated to the normal levels after GSP treatment.CONCLUSION: The renoprotective effect of GSP is associated with the down-regulation of GSTM through modulating the expression of Nrf2.更多还原