Ser473-Akt磷酸化介导阿托伐他汀保护大鼠脑缺血再灌注损伤  

Protective Effect of Ser473-Akt Phosphorylation Mediated Atorvastatin on Cerebral Ischemia-reperfusion Injury in Rats

作　　者：陶希[1] 卢伟[2] 胡治平[2] 宋涛[1] 邓景贵[1] 蔡华安[1] 王淑玲[1] 刘佳[1] 

机构地区：[1]湖南省马王堆医院康复医学科湖南省老年医学研究所,湖南长沙市410016 [2]中南大学湘雅二医院神经内科

出　　处：《中国康复理论与实践》2016年第6期655-659,共5页Chinese Journal of Rehabilitation Theory and Practice

基　　金：湖南省医药卫生科研计划项目(No.B2010-090)

摘　　要：目的探讨Akt之Ser473位点(Ser473-Akt)磷酸化在阿托伐他汀保护大鼠脑缺血再灌注损伤中的作用。方法 40只雄性Sprague-Dawley大鼠随机分成正常组(n=10)、假手术组(n=10)、缺血再灌注(I/R)组(n=10)和干预组(n=10)。采用线栓法制作大鼠脑缺血2 h再灌注72 h模型。正常组和假手术组不做任何处理,I/R组仅生理盐水灌胃,干预组在再灌注后大鼠苏醒时、24 h、48 h分别予生理盐水配制的阿托伐他汀10 mg/kg灌胃。72 h时处死所有大鼠,留取脑标本分别行HE染色及TUNEL染色,Western blotting检测脑前额叶皮质Akt及其Ser473-Akt表达。结果缺血再灌注72 h后,干预组神经细胞形态学变化较I/R组减轻;干预组凋亡阳性细胞数显著少于I/R组(t=-6.014,P<0.001);I/R组前额叶皮质Ser473-Akt较正常组和假手术组显著增加(t>20.327,P<0.001),而干预组明显高于I/R组(t=3.649,P=0.007)。结论 Ser473-Akt磷酸化在阿托伐他汀的神经细胞保护中起重要作用,通过抑制凋亡减轻大鼠脑缺血再灌注损伤。Objective To investigate the effect of Ser473-Akt phosphorylation in the protection of atorvastatin to cerebral ischemia-re- perfusion （I/R） injury in rats. Methods Forty male Sprague-Dawley rats were randomly divided into normal group （n=10）, sham group （n= 10）, FR group （n=10） and intervention group （n=10）. A model of cerebral ischemia-reperfusion in rats was establishied, with ischemia for 2 hours and reperfusion for 72 hours. The normal group and the sham group received no injury. I/R group was administered with normal saline only, and the intervention group received atorvastatin 10 mg/kg prepared with normal saline at palinesthesia, 24 and 48 hours after reperfu- sion. All rats were sacrificed 72 hours after reperfusion. HE staining and TUNEL staining were performed in the brain specimens. The ex- pression of Akt and Ser473-Akt in the prefrontal cortex of the brain were detected with Western blotting. Results Compared with I/R group, 72 hours after reperfusion, the damage of nerve cells significantly lessened in the intervention group; the apoptosis positive cells significant- ly reduced in the intervention group （t=-6.014, P〈0.001）. The expression of Ser473-Akt in prefrontal cortex was higher in I/R group than in the normal group and the sham group （t〉20.327, P〈0.001）, and was higher in the intervention group than in I/R group （t=-3.649, P=-0.007）. Conclusion The Ser473-Akt phosphorylation plays an important role in the protection of atorvastatin in nerve cell through anti-apoptosis of nerve cells, and reducing cerebral FR injury.

关 键 词：脑缺血/再灌注 Ser473-Akt 磷酸化 阿托伐他汀 细胞凋亡 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]