The role of autophagy in unilateral ureteral obstruction rat model
The role of autophagy in unilateral ureteral obstruction rat model
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DOI：
10.1111/j.1440-1797.2011.01541.x
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发表时间：
2012-02-01
期刊：
影响因子：
2.5
通讯作者：
Kim, Yong Kyun
中科院分区：
文献类型：
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作者：
Kim, Wan-Young;Nam, Sun Ah;Kim, Yong Kyun
目的：自噬是一种降解受损细胞质成分的细胞过程，调节细胞死亡或增殖。单侧输尿管梗阻（UUO）是一种在梗阻肾脏中进行性肾纤维化的模型。UUO后对侧肾细胞代偿性增生。我们研究了自噬在UUO后梗阻肾和对侧肾中的作用。方法：分别于UUO后3、7、14天处死大鼠，观察UUO时自噬的发生情况。为了检查自噬抑制剂3-甲基腺嘌呤（3-MA）的功效，每天腹膜内注射3-MA（30 mg/ kg/天）处理大鼠，持续7天。结果：UUO后，自噬在梗阻肾中以时间依赖的方式诱导。3-MA抑制自噬可增强UUO后梗阻肾中肾小管细胞凋亡和肾小管间质纤维化。在对侧肾脏中，自噬也在UUO期间被诱导和延长。用3-MA抑制自噬可显著增加UUO后对侧肾脏增殖细胞核抗原的蛋白表达。Akt-哺乳动物雷帕霉素靶蛋白（mTOR）信号通路参与了UUO后双肾自噬的诱导。结论：我们目前的研究结果支持UUO诱导的自噬在梗阻肾脏中具有肾脏保护作用，并通过AktmTOR信号通路调节对侧肾脏的代偿性细胞增殖。
Aim: Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death or proliferation. Unilateral ureteral obstruction (UUO) is a model of progressive renal fibrosis in the obstructed kidney. And UUO is followed by compensatory cellular proliferation in the contralateral kidney. We investigate the role of autophagy in the obstructed kidney and contralateral kidney after UUO. Methods: To obtain the evidence and the patterns of autophagy during UUO, the rats were sacrificed 3, 7 and 14 days after UUO. To examine the efficacy of the autophagy inhibitors, 3-methyladenine (3-MA), the rats were treated daily with intraperitoneal injection of 3-MA (30 mg/ kg per day) for 7 days. Results: After UUO, autophagy was induced in the obstructed kidney in a time-dependent manner. Inhibition of autophagy by 3-MA enhanced tubular cell apoptosis and tubulointerstitial fibrosis in the obstructed kidney after UUO. In the contralateral kidney, autophagy was also induced and prolonged during UUO. Inhibition of autophagy by 3-MA increased the protein expression of proliferating cell nuclear antigen significantly in the contralateral kidney after UUO. The Akt-mammalian target of rapamycin (mTOR) signalling pathway was involved in the induction of autophagy after UUO in both kidneys. Conclusion: Our present results support that autophagy induced by UUO has a renoprotective role in the obstructed kidney and regulatory role of compensatory cellular proliferation in the contralateral kidney through AktmTOR signalling pathway.