首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (3): 310-314.doi: 10.3969/j.issn.1006-7795.2014.03.010

• 脑血管病的基础研究 • 上一篇    下一篇

缺血后适应抑制大鼠脑缺血-再灌注后星形胶质细胞的增生

高志1, 赵海苹2, 罗玉敏2, 王荣亮2, 曾现伟1, 吉训明3   

  1. 1. 潍坊医学院外科学教研室, 山东潍坊 261053;
    2. 首都医科大学宣武医院脑血管病研究室, 北京 100053;
    3. 首都医科大学宣武医院神经外科, 北京 100053
  • 收稿日期:2014-02-17 出版日期:2014-06-21 发布日期:2014-06-14
  • 通讯作者: 吉训明,E-mail:jixm@ccmu.edu.cn E-mail:jixm@ccmu.edu.cn
  • 基金资助:

    国家自然科学基金(81201028,81071058,30770743)资助项目。

Ischemic postconditioning inhibited the proliferation of astrocyte following cerebral ischemia-reperfusion in rats

Gao Zhi1, Zhao Haiping2, Luo Yumin2, Wang Rongliang2, Zeng Xianwei1, Ji Xunming3   

  1. 1. Department of Surgery, Weifang Medical College, Weifang 261031, Shandong Province, China;
    2. Cerebrovascular Diseases Research Institute, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
    3. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • Received:2014-02-17 Online:2014-06-21 Published:2014-06-14
  • Supported by:

    This study was supported by National Natural Science Foundation of China(81201028, 81071058, 30770743).

摘要:

目的 观察缺血后适应(ischemia postconditioning,IPostC)对大鼠脑缺血-再灌注损伤后胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和组蛋白去乙酰化酶1(histone deacetylase1,HDAC1)表达变化,初步探讨IPostC对星形胶质细胞增生的影响。方法 采用线栓法制备大鼠短暂性大脑中动脉阻塞模型(transient middle cerebral occlusion,tMCAO)模型,采用抽签法将21只健康雄性Sprague Dawley(SD)大鼠(体质量280~300 g)随机分为7组,每组3只:1 假手术组(S);2 tMCAO 1h组(R-1h);3 tMCAO+IPostC 1h组(P-1h);4 tMCAO 4h组(R-4h);5 tMCAO+IPostC 4h组(P-4h);6 tMCAO 24h组(R-24h);7 tMCAO+IPostC 24h组(P-24h)。缺血后适应的具体操作是在拔除线栓后即刻用动脉阻断夹夹闭双侧颈总动脉,阻断血流10 s后恢复血流10 s,如此反复操作5次。分别应用Western blotting法和免疫荧光法研究大鼠脑缺血-再灌注及后适应1、4和24 h时HDAC1和GFAP表达的变化。结果 (1)Western blotting结果显示:1与S组相比,R组GFAP蛋白的表达均有所增加,R-1h和R-24h显著增加(P<0.05),P组的表达变化不大。与R组相比,P组GFAP的表达下降,其中P-4h组显著下降(P<0.05)。2与S组相比,R组HDAC1蛋白的表达均有所增加,其中R-1h显著增加(P<0.05),P组的表达变化不大。与R组相比,P组HDAC1的表达下降。(2)免疫荧光结果显示:HDAC1和GFAP蛋白有共定位,且HDAC1和GFAP的变化趋势同Western blotting结果相同。结论 IPostC可能通过降低HDAC1的表达来抑制星形胶质细胞的增生从而发挥对脑缺血-再灌注损伤的神经保护作用。

关键词: 脑缺血, 星形胶质细胞, 缺血后适应, 组蛋白去乙酰化酶1, 大鼠

Abstract:

Objective To observe the effect of ischemic postconditioning(IPostC) on histone deacetylase 1(HDAC1) and glial fibrillary acidic protein(GFAP) expression induced by cerebral ischemia-reperfusion injury in rats, and preliminarily explore the effect of IPostC on proliferation of astrocyte. Methods Transient middle cerebral occlusion(tMCAO) operation was performed by using suture method. A total of 21 male Sprague-Dawley(SD) rats(280-300 g) were randomly divided into 7 groups: 1 Sham group(S); 2 tMCAO 1 h group(R-1h); 3 tMCAO+IPostC 1 h group(P-1h); 4 tMCAO 4 h group(R-4h); 5 tMCAO+IPostC 4 h group(P-4h); 6 tMCAO 24 h group(R-24h); 7 tMCAO+IPostC 24 h group(P-24h). In the tMCAO+IPostC groups, IPostC was carried out by five cycles of 10 s occlusion/10 s release of the bilateral common carotid arteries using clamps immediately after reperfusion. Western blotting and immunofluorescence staining were used to observe the expression levels of HDAC1 and GFAP. Results Western blotting results showed that compared with the S group, the GFAP protein expression was increased in R groups and those in the R-1h and R-24h groups were statistically significantly increased(P<0.05). The GFAP protein expression in P groups did not change significantly. Compared with the R group, the GFAP protein expression was reduced in P groups and that in the P-4h group was statistically significantly reduced(P<0.05). Compared with the S group, the HDAC1 protein expression was increased in R groups and that in the R-1h group was statistically significantly increased(P<0.05). The HDAC1 protein expression in P groups did not change significantly. Compared with the R group, the HDAC1 protein expression in P groups was reduced clearly. The immunofluorescence staining results showed that HDAC1 was colocated with GFAP, and also were consistent with those of the Western blotting. Conclusion IPostC decreased the proliferation of astrocyte probably through decreasing HDAD1, therefore, to play a protective role in the ischemia-reperfusion injured brain.

Key words: cerebral ischemia, astrocyte, ischemic postconditioning, histone deacetylase1, rats

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