Zeng Zhenhua, Chen Zhongqing, Xu Siqi, Song Rui, Yang Hong, Zhao Ke-seng
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China ; Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Oxid Med Cell Longev. 2015;2015:965961. doi: 10.1155/2015/965961. Epub 2015 Aug 2.
To evaluate the role of SIRT1 in small intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment.
The severe hemorrhagic shock model was reproduced in Sprague Dawley rats.
Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection.
Bleeding and swelling appeared in the small intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1.
The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small intestine injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment.
评估SIRT1在严重失血性休克后小肠损伤中的作用，并研究白藜芦醇苷（PD）在休克治疗中是否能激活SIRT1。
在Sprague Dawley大鼠中复制严重失血性休克模型。
给药2小时后，一半大鼠用于评估生存时间，其余大鼠用于收集小肠组织样本。
失血性休克期间，小肠出现出血、肿胀，伴有上皮细胞凋亡和肠屏障紊乱。小肠的SIRT1活性和PGC-1α蛋白表达降低，导致乙酰化SOD2增加，SOD2的表达和活性降低，从而导致严重的氧化应激。PD给药组中降低的SIRT1活性和表达部分恢复，表现为肠损伤减轻和生存时间延长。值得注意的是，添加SIRT1选择性抑制剂Ex527后，PD的作用被消除。
这些结果共同表明SIRT1-PGC-1α-SOD2轴在严重失血性休克后小肠损伤中起作用，且PD是休克治疗中一种有效的SIRT1激活剂。
