《中国康复理论与实践》

《中国康复理论与实践》

• 基础研究 • 上一篇    下一篇

Ser473-Akt 磷酸化介导阿托伐他汀保护大鼠脑缺血再灌注损伤①

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   

  1. 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，湖南长沙市410011。
  • 出版日期:2016-06-25 发布日期:2016-07-04

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

TAO Xi1, LU Wei2, HU Zhi-ping2, SONG Tao1, DENG Jing-gui1, CAI Hua-an1, WANG Shu-ling1, LIU Jia1   

  1. 1. Department of Rehabilitation Medicine, Mawangdui Hospital of Hunan Province, Changsha, Hunan 410016, China; 2. the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
  • Published:2016-06-25 Online:2016-07-04

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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。

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

Abstract: Objective To investigate the effect of Ser473-Akt phosphorylation in the protection of atorvastatin to cerebral ischemia-reperfusion (I/R) injury in rats. Methods Forty male Sprague-Dawley rats were randomly divided into normal group (n=10), sham group (n= 10), I/R 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 reperfusion. All rats were sacrificed 72 hours after reperfusion. HE staining and TUNEL staining were performed in the brain specimens. The expression 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 significantly 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 I/R injury.

Key words: cerebral ischemia-reperfusion, Ser473-Akt, phosphorylation, atorvastatin, apoptosis, rats