Salidroside protects rat liver against ischemia/reperfusion injury by regulating the GSK-3β/Nrf2-dependent antioxidant response and mitochondrial permeability transition
Salidroside protects rat liver against ischemia/reperfusion injury by regulating the GSK-3β/Nrf2-dependent antioxidant response and mitochondrial permeability transition
复制标题
红景天苷通过调节 GSK-3 beta/Nrf2 依赖性抗氧化反应和线粒体通透性转变来保护大鼠肝脏免受缺血/再灌注损伤
DOI：
10.1016/j.ejphar.2017.04.011
复制
发表时间：
2017-07-05
影响因子：
5
通讯作者：
Fu, Hailong
中科院分区：
文献类型：
--
作者：
Cai, Linlin;Li, Yonghua;Fu, Hailong
红景天苷（Salidroside，Sal）是一种天然抗氧化剂，在体内和体外均具有心脏保护和神经保护作用，但其对肝脏缺血/再灌注损伤的影响尚不清楚。本研究旨在探讨红景天苷对大鼠节段性（70%）热肝I/R损伤的保护作用。将动物随机分为假手术组、假手术+红景天苷预处理组（Sal）、假手术+红景天苷+羧甲基红景天苷组（CATR）、假手术+CATR组、I/R组、I/R+Sal组、I/R+Sal+CATR组和I/R+CATR组。将肝动脉、左门静脉和肝中叶闭塞60分钟，然后松开以允许再灌注。红景天苷预处理（20 mg/kg/天，7天，腹腔注射）显着降低血清丙氨酸氨基转移酶（sALT）和血清天冬氨酸氨基转移酶（sAST）水平后6小时和24小时的再灌注和保护肝脏对I/R诱导的损伤。然而，这种保护作用可以逆转CATR，线粒体渗透性转换孔（MPTP）开放剂（5毫克/公斤30分钟前，I/R损伤，腹腔内）。机制研究表明，红景天苷抑制糖原合成酶激酶-3 β（GSK-3 β）活性，并通过激活Akt信号通路增强NF-E2相关因子（Nrf 2）依赖性抗氧化反应，从而减少线粒体活性氧的产生，增加MPTP抗性，并通过抑制再灌注期间细胞色素c释放和半胱天冬酶激活来防止细胞凋亡。因此，红景天苷通过激活GSK-3 β/Nrf 2依赖性抗氧化反应和随后的MPTP抑制来改善肝细胞死亡和凋亡。这些结果为红景天苷在外科手术中的保肝作用提供了实验依据。
Salidroside (Sal) is a natural antioxidant that elicits cardioprotective and neuroprotective effects in vivo and in vitro; however, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. The purpose of this study was to investigate the hepatoprotective effects of salidroside against segmental (70%) warm hepatic I/R injury in rats. Animals were randomized into Sham, Sham+salidroside pretreatment (Sal), Sham+Sal +carboxyatractyloside (CATR), Sham+CATR, I/R, I/R+Sal, I/R+Sal+CATR and I/R+CATR groups. The hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then undamped to allow reperfusion. Pretreatment with salidroside (20 mg/kg/day for 7 days, intraperitoneally) significantly decreased serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) levels after 6 h and 24 h of reperfusion and protected the liver against I/R-induced injury. However, this protective effect could be reversed by CATR, a mitochondrial permeability transition pore (MPTP) opener (5 mg/kg 30 min before I/R insult, intraperitoneally). Mechanistic studies have revealed that salidroside inhibits glycogen synthase kinase-3 beta (GSK-3 beta) activity and enhances the NF-E2-related factor (Nrf2)-dependent antioxidant response by activating the Akt signaling pathway, thereby reducing mitochondrial reactive oxygen species generation, increasing MPTP resistance and preventing apoptosis by suppressing cytochrome c release and caspase activation during reperfusion. Therefore, salidroside ameliorates hepatocyte death and apoptosis through activation of the GSK-3 beta/Nrf2-dependent antioxidant response and subsequent MPTP inhibition. These results provide experimental evidence supporting the clinical use of salidroside for hepatoprotection in surgical settings.