Glutamine ameliorates intestinal ischemia-reperfusion Injury in rats by activating the Nrf2/Are signaling pathway.
Glutamine ameliorates intestinal ischemia-reperfusion Injury in rats by activating the Nrf2/Are signaling pathway.
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发表时间：
2015-07
影响因子：
1.4
通讯作者：
Aili Wang;Qiong Niu;Ning Shi;Jian Wang;Xingfang Jia;Haifeng Lian;Zhiqiang Liu;Cheng-Xia Liu
中科院分区：
文献类型：
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作者：
Aili Wang;Qiong Niu;Ning Shi;Jian Wang;Xingfang Jia;Haifeng Lian;Zhiqiang Liu;Cheng-Xia Liu
缺血再灌注（I/R）介导的肠粘膜损伤通常是由再灌注后黄嘌呤氧化酶系统产生的氧源性毒性自由基引起的，但谷氨酰胺保护肠粘膜的详细分子机制尚不清楚。本研究旨在阐明谷氨酰胺是否可以预防大鼠I/R后肠粘膜的损伤，并在大鼠模型中研究GLN诱导的Nrf 2/ARE通路的信号传导。我们的结果表明，谷氨酰胺预处理可减轻I/R引起的空肠损伤和微血管通透性增高。与假手术组和GLN I/R组相比，I/R组MDA含量显著升高，SOD和GSH-Px含量显著降低。与I/R组相比，GLN预处理显著升高Nrf 2和HO-1的mRNA和蛋白水平。GLN处理还升高Bcl-2水平，并相应地抑制空肠细胞中的凋亡损伤，所述凋亡损伤通过降低裂解的半胱天冬酶-3水平显示。机制研究表明，GLN处理增强了Nrf 2与Bcl 2基因启动子的结合。这些结果表明，谷氨酰胺通过激活Nrf 2/ARE信号通路抑制ROS产生和减少肠细胞凋亡对I/R具有保护作用。
Ischemia-reperfusion (I/R)-mediated intestinal mucosal injury is usually induced by oxygen-derived toxic free radicals from the xanthine oxidase system after reperfusion, but the detailed molecular mechanisms underlying glutamine protection is still unclear. This study aims to elucidate whether glutamine prevents damage to the intestinal mucosa after I/R in rats and to investigate signaling by the Nrf2/ARE pathway induced by GLN in a rat model. Our results revealed that Glutamine pretreatment reduced jejunum injury and microvascular hyper-permeability induced by I/R. MDA level significantly increased while the SOD and GSH-Px levels decreased in the I/R group compared to the sham group and the GLN-I/R group. Both the mRNA and protein levels of the Nrf2 and HO-1 were significantly elevated by GLN pretreatment when compared to the I/R group. GLN treatment also elevated Bcl-2 levels, and accordingly suppressed apoptotic damage in the jejunum cells shown by decreased cleaved caspase-3 level. Mechanistic investigation revealed that GLN treatment augmented binding of Nrf2 onto Bcl2 gene promoter. These results indicate that glutamine has protective effects on I/R in vivo by activating the Nrf2/ARE signaling pathway to inhibit ROS production and reduce intestinal apoptosis.