二甲双胍对大鼠肾缺血再灌注损伤后纤维化的影响  

Effect of Metformin on tubulointerstitial fibrosis following renal ischemia-reperfusion injury in rats

作　　者：苏娟[1] SU Juan(Department of Gastroenterology,Renmin Hospital of Wuhan University,Hubei Province,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院消化内科一科,湖北武汉430060

出　　处：《中国医药导报》2018年第22期22-26,183,共6页China Medical Herald

摘　　要：目的探讨二甲双胍对大鼠肾脏缺血再灌注后纤维化改变的保护作用。方法采用随机数字表法将24只SD雄性成年大鼠分为假手术(Sham)组、缺血再灌注(I/R)组和二甲双胍(Metformin)处理组,每组8只。再灌注12周后,检测各组大鼠血清肌酐(Cr)、尿素氮(BUN)水平,苏木精-伊红(HE)染色和Masson染色观察肾组织结构变化和纤维化改变;免疫组织化学观察α-平滑肌肌动蛋(α-SMA)和转化生长因子-β_1(TGF-β_1)分布;Western blot进一步检测α-SMA和TGF-β_1的表达水平。结果 Sham组、I/R组和Metformin组间Cr和BUN比较差异无统计学意义(P>0.05)。与Sham组比较,I/R组和Metformin组大鼠肾脏出现了明显间质纤维化,但是Metformin组与I/R组比较肾脏间质纤维化明显减轻;与Sham组比较,I/R组和Metformin组大鼠肾脏α-SMA和TGF-β_1的表达水平显著升高,Metformin组与I/R组比较,大鼠肾脏α-SMA和TGF-β_1的表达水平显著降低;差异均有高度统计学意义(P<0.01)。结论肾脏缺血再灌注损伤可以引起小管间质纤维化,二甲双胍处理可以减轻此病理改变,其作用可能与二甲双胍能够抑制α-SMA和TGF-β_1表达相关。Objective To assess the potential effects of Metformin on the development of tubulointerstitial fibrosis after acute renal ischemia-reperfusion.Methods Twenty-four male Sprague Dawley rats were randomly assigned to three groups:Sham group,I/R group and Metformin group(n=8).Twelve weeks after reperfusion,levels of serum urea nitrogen(BUN)and creatinine(Cr)were assessed;Hematoxylin-eosin(H&E)and Masson′s trichrome staining were used to assess renal fibrosis;the expression spot and protein levels ofα-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)were analyzed by immunohistochemistry(IHC)and Western blot.Results There was no statistically significant difference in levels of Cr and BUN among Sham group,I/R group and Metformin group(P>0.05).Compared with the Sham group,tubulointerstitial fibrosis was more obvious in the I/R group and the Metformin group;however,the level of tubulointerstitial fibrosis in the Metformin group was less than that of the I/R group.Compared with the Sham group,the levels ofα-SMA and TGF-β1 were significantly increased in the I/R group and the Metformin group,the expression ofα-SMA and TGF-β1 in the Metformin group were significantly decreased compared with those in the I/R group;the differences were statistically significant(P<0.01).Conclusion Administration of metformin significantly attenuated tubuleinterstitial fibrosis following I/R in rats,potentially via down-regulating expressions ofα-SMA and TGF-β1.

关 键 词：缺血再灌注损伤 二甲双胍 肾 纤维化 

分 类 号：R692.6[医药卫生—泌尿科学]