Ischemic Postconditioning Inhibits the Renal Fibrosis Induced by Ischemia-reperfusion Injury in Rats
Ischemic Postconditioning Inhibits the Renal Fibrosis Induced by Ischemia-reperfusion Injury in Rats
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DOI：
10.1016/j.urology.2012.02.054
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发表时间：
2012-08-01
期刊：
影响因子：
2.1
通讯作者：
Chen, Hui
中科院分区：
文献类型：
--
作者：
Weng, Xiaodong;Shen, Hao;Chen, Hui
目的探讨缺血后处理对急性肾缺血再灌注后肾小管间质纤维化的影响。方法采用右肾切除后夹闭左蒂45分钟建立大鼠肾缺血再灌注模型，无论是否进行缺血后处理，再灌注12周。苏木精-伊红 (H&E) 和马森三色染色用于评估肾纤维化。还分析了α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）和磷酸-Smad2的表达点和蛋白水平。 结果我们的数据显示，12周后，单独接受I/R或后处理的大鼠中发现斑片状炎症和肾小管间质纤维化。进行 45 分钟缺血再灌注的大鼠中，肾小管间质纤维化进一步恶化，并伴随着 12 周结束时 α-SMA、TGF-β 1 和磷酸化 Smad2 表达的增加。相比之下，缺血后处理组大鼠上述组织学变化和分子表达明显减弱。结论：45分钟I/R损伤可能导致长期肾小管间质纤维化，缺血后处理对肾纤维化有有益作用。其机制可能涉及抑制TGF-β1/磷酸化Smad2通路从而发挥保护作用。泌尿学 80：484.e1-484.e7，2012。(c) 2012 Elsevier Inc.
OBJECTIVE To investigate whether ischemic postconditioning effects on the development of tubulointerstitial fibrosis follow acute renal ischemia-reperfusion.METHODS Rat models of warm renal I/R were established by clamping left pedicles for 45 minutes after right nephrectomy, both with and without treatment with ischemic postconditioning, and then reperfused for up to 12 weeks. Hematoxylin-eosin (H&E) and Masson's trichrome staining were used to assess renal fibrosis. The expression spot and protein levels of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta 1 (TGF-beta 1), and phospho-Smad2 were also analyzed.RESULTS Our data showed that patchy inflammation and tubulointerstitial fibrosis were found 12 weeks later in rats subjected to I/R alone or with postconditioning. Tubulointerstitial fibrosis worsened further in rats subjected to 45-minute ischemia-reperfusion, accompanied by the increased expressions of alpha-SMA, TGF-beta 1, and phospho-Smad2 at the end of 12 weeks. In contrast, the above histologic changes and molecular expressions were significantly attenuated in rats of ischemic postconditioning group.CONCLUSION The results indicated that 45-minute I/R injury may cause tubulointerstitial fibrosis in the long term, and ischemic postconditioning has beneficial effects on renal fibrosis. Its mechanisms may involve inhibition of the TGF-beta 1/phospho-Smad2 pathway to exert protective effects. UROLOGY 80: 484.e1-484.e7, 2012. (c) 2012 Elsevier Inc.