Jang Hee-Seong, Kim Jee In, Kim Jinu, Park Jeen-Woo, Park Kwon Moo
Department of Anatomy and BK21 Plus Biomedical Convergence Program, Cardiovascular Research Institute, Kyungpook National University School of Medicine, 101 Dongin-dong Jung-gu, Daegu 700-422, Republic of Korea.
Department of Molecular Medicine and ODR Medical Research Center, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
Biomed Res Int. 2014;2014:602149. doi: 10.1155/2014/602149. Epub 2014 Aug 28.
Ischemic preconditioning (IPC) by ischemia/reperfusion (I/R) renders resistance to the kidney. Strong IPC triggers kidney fibrosis, which is involved in angiotensin II (AngII) and its type 1 receptor (AT1R) signaling. Here, we investigated the role of AngII/AT1R signal pathway in the resistance of IPC kidneys to subsequent I/R injury. IPC of kidneys was generated by 30 minutes of bilateral renal ischemia and 8 days of reperfusion. Sham-operation was performed to generate control (non-IPC) mice. To examine the roles of AngII and AT1R in IPC kidneys to subsequent I/R, IPC kidneys were subjected to either 30 minutes of bilateral kidney ischemia or sham-operation following treatment with AngII, losartan (AT1R blocker), or AngII plus losartan. IPC kidneys showed fibrotic changes, decreased AngII, and increased AT1R expression. I/R dramatically increased plasma creatinine concentrations in non-IPC mice, but not in IPC mice. AngII treatment in IPC mice resulted in enhanced morphological damage, oxidative stress, and inflammatory responses, with functional impairment, whereas losartan treatment reversed these effects. However, AngII treatment in non-IPC mice did not change I/R-induced injury. AngII abolished the resistance of IPC kidneys to subsequent I/R via the enhancement of oxidative stress and inflammatory responses, suggesting that the AngII/AT1R signaling pathway is associated with outcome in injury-experienced kidney.
缺血/再灌注（I/R）诱导的缺血预处理（IPC）使肾脏产生抗性。强烈的IPC会引发肾纤维化，这与血管紧张素II（AngII）及其1型受体（AT1R）信号传导有关。在此，我们研究了AngII/AT1R信号通路在IPC肾脏对后续I/R损伤的抗性中的作用。通过双侧肾脏缺血30分钟和再灌注8天来产生肾脏IPC。进行假手术以制备对照（非IPC）小鼠。为了研究AngII和AT1R在IPC肾脏对后续I/R中的作用，在用AngII、氯沙坦（AT1R阻滞剂）或AngII加氯沙坦处理后，对IPC肾脏进行30分钟的双侧肾脏缺血或假手术。IPC肾脏呈现纤维化改变、AngII减少以及AT1R表达增加。I/R显著增加了非IPC小鼠的血浆肌酐浓度，但在IPC小鼠中未增加。对IPC小鼠进行AngII处理导致形态学损伤、氧化应激和炎症反应增强，并伴有功能损害，而氯沙坦处理则逆转了这些效应。然而，对非IPC小鼠进行AngII处理并未改变I/R诱导的损伤。AngII通过增强氧化应激和炎症反应消除了IPC肾脏对后续I/R的抗性，这表明AngII/AT1R信号通路与经历过损伤的肾脏的损伤结局相关。
