Ischemic postconditioning attenuates acute kidney injury following intestinal ischemia-reperfusion through Nrf2-regulated autophagy, anti-oxidation, and anti-inflammation in mice

被引：22

作者：

Chen, Rong ^{[1
]}

Zeng, Zi ^{[1
]}

Zhang, Yun-yan ^{[1
]}

Cao, Chen ^{[2
]}

Liu, Hui-min ^{[1
]}

Li, Wei ^{[1
]}

Wu, Yang ^{[1
]}

Xia, Zhong-yuan ^{[1
]}

Ma, Daqing ^{[3
]}

Meng, Qing-tao ^{[1
]}

机构：

[1] Wuhan Univ, Dept Anesthesiol, Renmin Hosp, Wuhan 430060, Peoples R China

[2] 3rd Hosp Wuhan, Dept Endocrinol, Wuhan, Peoples R China

[3] Imperial Coll London, Chelsea & Westminster Hosp, Div Anaesthet Pain Med & Intens Care, Dept Surg & Canc,Fac Med, London, England

来源：

FASEB JOURNAL | 2020年 / 34卷 / 07期

基金：

中国国家自然科学基金;

关键词：

acute kidney injury; autophagy; intestinal ischemia-reperfusion; ischemic postconditioning; Nrf2; HO-1; pathway; ACUTE LUNG INJURY; CEREBRAL-ISCHEMIA; CARDIAC-SURGERY; NRF2; PROTECTS; DAMAGE; DEFENSE; CANCER; RATS;

D O I：

10.1096/fj.202000274R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Intestinal ischemia-reperfusion (IIR) often occurs during and following major cardiovascular or gut surgery and causes significant organ including kidney injuries. This study was to investigate the protective effect of intestinal ischemic postconditioning (IPo) on IIR-induced acute kidney injury (AKI) and the underling cellular signaling mechanisms with focus on the Nrf2/HO-1. Adult C57BL/6J mice were subjected to IIR with or without IPo. IIR was established by clamping the superior mesenteric artery (SMA) for 45 minutes followed by 120 minutes reperfusion. Outcome measures were: (i) Intestinal and renal histopathology; (ii) Renal function; (iii) Cellular signaling changes; (iv) Oxidative stress and inflammatory responses. IPo significantly attenuated IIR-induced kidney injury. Furthermore, IPo significantly increased both nuclear Nrf2 and HO-1 expression in the kidney, upregulated autophagic flux, inhibited IIR-induced inflammation and reduced oxidative stress. The protective effect of IPo was abolished by the administration of Nrf2 inhibitor (Brusatol) or Nrf2 siRNA. Conversely, a Nrf2 activator t-BHQ has a similar protective effect to that of IPo. Our data indicate that IPo protects the kidney injury induced by IIR, which was likely mediated through the Nrf2/HO-1 cellular signaling activation.

引用

页码：8887 / 8901

页数：15