Diverse Effects of Ischemic Pretreatments on the Long-Term Renal Damage Induced by Ischemia-Reperfusion
Diverse Effects of Ischemic Pretreatments on the Long-Term Renal Damage Induced by Ischemia-Reperfusion
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缺血预处理对缺血再灌注引起的长期肾损伤的不同影响
DOI：
10.1159/000239574
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发表时间：
2009-01-01
影响因子：
4.2
通讯作者：
Ding, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Jiang, Suhua;Chen, Yue;Ding, Xiaoqiang
背景/目的：缺血预处理在肾缺血再灌注（I/R）损伤后长期变化中的作用仍不清楚。在本研究中，我们的主要目的是探讨不同持续时间的缺血预处理对急性肾缺血再灌注后肾小管间质纤维化和功能损害的影响。方法：建立大鼠肾热I/R模型，夹闭双蒂40 min，再灌注；实验进行了 10 周的随访。在 40 分钟缺血之前 8 天诱导先前的缺血（10、20、30 分钟）。为了评估组织纤维化，我们进行了形态测量分析、马森三色和天狼星红染色。我们还分析了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。结果：5 周和 10 周后，仅接受 I/R 或经过 10 分钟缺血预处理的大鼠发现斑片状肾小管间质纤维化。缺血30分钟预处理的大鼠肾小管间质纤维化进一步恶化，并出现肾功能障碍，并伴随着5周时α-SMA、TGF-β1和磷酸化Smad2表达的增加。相比之下，在经过 20 分钟缺血预处理的大鼠中，上述异常现象显着减弱。结论：严重I/R损伤可能导致长期肾小管间质纤维化，不同缺血预处理对肾纤维化的影响不同。
Background/Aims: The role of ischemic pretreatment in long-term changes after renal ischemia-reperfusion (I/R) injury remains unknown. In this study, we mainly aimed to investigate the effect of ischemic pretreatments with different durations on the development of tubulointerstitial fibrosis and functional impairment following acute renal I/R. Methods: We established a rat model of renal warm I/R, clamping both pedicles for 40 min followed by reperfusion; the experiment was followed up for 10 weeks. Prior ischemia (10, 20, 30 min) was induced 8 days before the 40-min ischemia. To assess tissue fibrosis, we performed morphometric analysis, Masson’s trichrome and Sirius red staining. We also analyzed the expression of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and phospho-Smad2. Results: Patchy tubulointerstitial fibrosis was found 5 and 10 weeks later in rats subjected to I/R alone or pretreated with 10-min ischemia. Tubulointerstitial fibrosis deteriorated further and renal dysfunction occurred in rats pretreated with 30-min ischemia accompanied by increased expression of α-SMA, TGF-β1, and phospho-Smad2 at 5 weeks. In contrast, the above abnormalities were significantly attenuated in rats pretreated with 20-min ischemia. Conclusion: Severe I/R injury may cause tubulointerstitial fibrosis in the long term, and different ischemic pretreatments have diverse effects on renal fibrosis.