二甲双胍对大鼠肾缺血再灌注损伤后纤维化的影响

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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-β1（TGF-β1）分布；Western blot进一步检测α-SMA和TGF-β1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-β1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-β1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-β1表达相关。

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	苏娟

关键词 ：缺血再灌注损伤, 二甲双胍, 肾, 纤维化

Abstract：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 of α-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 of α-SMA and TGF-β1 were significantly increased in the I/R group and the Metformin group, the expression of α-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 of α-SMA and TGF-β1.

Key words： Ischemia-reperfusion injury Metformin Renal Fibrosis

引用本文:

苏娟. 二甲双胍对大鼠肾缺血再灌注损伤后纤维化的影响[J]. 中国医药导报, 2018, 15(22): 22-26.
SU Juan. Effect of Metformin on tubulointerstitial fibrosis following renal ischemia-reperfusion injury in rats. 中国医药导报, 2018, 15(22): 22-26.

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