富氢液通过PI3K通路减轻大鼠脑缺血再灌注损伤  

Hydrogen-rich saline reduces cerebral ischemia-reperfusion injury in rats via PI3K pathway

作　　者：陈克研[1] 董婉维[1] CHEN Ke-yan DONG Wan-wei(Department of Laboratory Animal Science, China Medical University, Shenyang 110001, China)

机构地区：[1]中国医科大学实验动物部,沈阳110001

出　　处：《中国比较医学杂志》2017年第7期13-16,33,共5页Chinese Journal of Comparative Medicine

基　　金：国家自然青年科学基金项目(31201758);中国医科大学新教师基金项目(XZR20160036)

摘　　要：目的探讨富氢液对大鼠脑缺血再灌注致海马神经元凋亡及PI3K/Akt/FoxO1信号通路表达的影响。方法采用线栓法阻塞大鼠大脑中动脉,建立大鼠局灶性脑缺血/再灌注(I/R)模型,SD大鼠随机分为假手术组(Sham组)、缺血/再灌注组(I/R组)和富氢液处理组(HRS组),每组10只;各组于再灌注后24 h,ELISA检测血清中炎症因子IL-6、TNF-α及IL-1β的变化;HE染色观察海马变化,TUNEL法观察脑组织细胞凋亡情况;Western blot法检测海马p-PI3K、Akt、caspase-3和FoxO1蛋白表达变化。结果与Sham组相比,I/R组锥体细胞排列疏松,大量锥体细胞死亡,海马凋亡细胞增多,血清炎症因子IL-1β、IL-6、TNF-α、表达显著增加(P<0.05),脑组织中pPI3K、Akt、caspase-3表达显著升高,FoxO1蛋白降低,两组间比较均具有统计学差异(P<0.05);与I/R组相比,HRS组炎症因子显著降低;p-PI3K、Akt、caspase-3表达水平均显著降低,,FoxO1蛋白升高(P<0.05)。结论富氢液可以减轻缺血再灌注导致的脑损伤,其机制可能与PI3K/Akt/FoxO1信号通路相关。Objective To investigate the effect of hydrogen-rich saline on apoptosis in hippocampal neurons induced by cerebral ischemia-reperfusion in rats and PI3K/Akt/FoxO1 signaling pathway. Methods The rat model of focal cerebral ischemia-reperfusion was established by thread-occlusion of the middle cerebral artery in rats. SD rats were randomly divided into sham operation group （ Sham group）, ischemia-reperfusion group （ I/R group） and hydrogen-rich saline treatment group （HRS group） , 10 rats in each group. At 24 h after reperfusion, the serum levels of IL-6, TNF-a and IL-113 were detected by ELISA. Histological changes of the hippocampus were observed by pathology using HE staining. Apoptosis in brain tissues was observed by TUNEL staining. The expression changes of p-PI3K, Akt, caspase-3 and FoxO1 proteins were detected by Western blot assay. Results Compared with the sham group, pyramidal cells were arranged loosely in the I/R group and a large number of pyramidal cells were necrotized, and the amount of apoptotic hippocampal cells was increased. The levels of IL-1α, IL-6 and TNF-α were significantly increased （P 〈 0. 05） , as well as the expression of p-PI3K, Akt and caspase-3 in the brain tissue. However, the expression of FoxO1 protein was decreased. There were significant differences between the two groups （P 〈 0. 05）. Compared with the I/R group, the inflammatory factors were significantly decreased in the HRS group. The expressions of p-PI3K, Akt and caspase-3 were also significantly decreased, while the expression of FoxO1 protein was increased （P 〈 0.05）. Conclusions Hydrogen- rich saline can reduce brain injury caused by ischemia-reperfusion, and its mechanism may be related to PI3K/Akt/FoxO1 signaling pathway.

关 键 词：富氢液 缺血再灌注 PI3K FOXO1 细胞凋亡 

分 类 号：R-33[医药卫生]