Proteomic analysis of intestinal ischemia/reperfusion injury and ischemic preconditioning in rats reveals the protective role of aldose reductase
Proteomic analysis of intestinal ischemia/reperfusion injury and ischemic preconditioning in rats reveals the protective role of aldose reductase
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DOI：
10.1002/pmic.201000078
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发表时间：
2010-12-01
期刊：
影响因子：
3.4
通讯作者：
Huang, Wen-Qi
中科院分区：
文献类型：
--
作者：
Liu, Ke-Xuan;Li, Cai;Huang, Wen-Qi
肠缺血/再灌注（I/R）损伤是一种与高发病率和死亡率相关的危重疾病。研究表明，缺血预处理（IPC）对肠I/R损伤具有保护作用。然而，这一事件的潜在分子机制尚未完全阐明。本研究采用双向电泳结合基质辅助激光解吸电离质谱技术（MALDI-MS）对缺血再灌注损伤大鼠肠粘膜蛋白质组进行了分析。肠I/R后肠粘膜中有16种蛋白质含量变化超过1.5倍。这些蛋白质分别参与细胞能量代谢、抗氧化和抗凋亡过程。这些蛋白质之一，醛糖还原酶（AR），去除活性氧。RT-PCR和western blot分析证实，缺血再灌注损伤后AR mRNA和蛋白表达显著下调，IPC处理后AR mRNA和蛋白表达增强。进一步的研究表明，AR选择性抑制剂依帕司他完全逆转了IPC的保护作用，表明IPC主要通过增加肠AR表达来保护肠I/R损伤。AR可能在肠缺血保护中起关键作用，这一发现可能为开发新的肠I/R损伤治疗方法提供依据。
Intestinal ischemia/reperfusion (I/R) injury is a critical condition associated with high morbidity and mortality. Studies show that ischemic preconditioning (IPC) can protect the intestine from I/R injury. However, the underlying molecular mechanisms of this event have not been fully elucidated. In the present study, 2-DE combined with MALDI-MS was employed to analyze intestinal mucosa proteomes of rat subjected to I/R injury in the absence or presence of IPC pretreatment. The protein content of 16 proteins in the intestinal mucosa changed more than 1.5-fold following intestinal I/R. These proteins were, respectively, involved in the cellular processes of energy metabolism, anti-oxidation and anti-apoptosis. One of these proteins, aldose reductase (AR), removes reactive oxygen species. In support of the 2-DE results, the mRNA and protein expressions of AR were significantly downregulated upon I/R injury and enhanced by IPC as confirmed by RT-PCR and western blot analysis. Further study showed that AR-selective inhibitor epalrestat totally turned over the protective effect of IPC, indicating that IPC confers protection against intestinal I/R injury primarily by increasing intestinal AR expression. The finding that AR may play a key in intestinal ischemic protection might offer evidences to foster the development of new therapies against intestinal I/R injury.