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缺血预处理对肾缺血再灌注损伤中全身及肾脏血流动力学变化的影响。

Effects of ischemic preconditioning on the systemic and renal hemodynamic changes in renal ischemia reperfusion injury.

作者信息

Ge Yu-Zheng, Wu Ran, Xin Hui, Liu Hao, Lu Tian-Ze, Zhao You-Cai, Shen Jiang-Wei, Hu Zhi-Kai, Yu Peng, Zhou Liu-Hua, Xu Lu-Wei, Xu Zheng, Wu Jian-Ping, Li Wen-Cheng, Zhu Jia-Geng, Jia Rui-Peng

机构信息

Department of Urology, Nanjing First Hospital, Nanjing Medical University 68 Changle Road, Nanjing 210006, China ; Center for Renal Transplantation, Nanjing First Hospital, Nanjing Medical University 68 Changle Road, Nanjing 210006, China.

Department of Urology, The Second Affiliated Hospital of Zhejiang University School of Medicine 88 Jiefang Road, Hangzhou 310009, China.

出版信息

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1128-40. eCollection 2015.

Abstract

BACKGROUND

Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO).

METHODS

Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion.

RESULTS

IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME.

CONCLUSIONS

The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.

摘要

背景

缺血预处理(IPC)可预防随后的肾缺血再灌注损伤(IRI)。然而,IPC的潜在机制仍远未完全明确。因此,我们探讨了IPC对肾脏和全身血流动力学变化、肾功能和形态的影响,以及内皮型和诱导型一氧化氮合酶(eNOS/iNOS)和一氧化氮(NO)的作用。

方法

雄性Sprague-Dawley大鼠在右侧肾切除术后随机分为五组:假手术组(手术但不夹闭血管);IRI组(左肾动脉夹闭45分钟);IPC组(预处理15分钟缺血和10分钟再灌注);IPC + 溶媒组(IPC前5分钟给予0.9%生理盐水);IPC + N(G)-硝基-L-精氨酸甲酯(L-NAME)组(IPC前5分钟用L-NAME预处理)。在再灌注后的指定时间点测量肾脏和全身血流动力学参数、肾功能和形态,以及肾脏中eNOS、iNOS和NO的表达水平。

结果

IPC组大鼠的肾功能、形态和肾动脉血流量(RABF)有显著改善,对全身血流动力学和肾静脉血流量无明显影响。再灌注24小时后,IPC组大鼠肾脏中eNOS、iNOS和NO的表达水平升高。此外,给予L-NAME可完全消除这些有益作用。

结论

结果表明,IPC可能通过eNOS/iNOS介导的NO生成促进RABF的早期恢复,从而减轻IRI所致的肾功能障碍和组织学损伤。

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