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辛伐他汀对大鼠脑出血后的半胱氨酸蛋白酶7和凋亡抑制蛋白1表达变化的影响
作者:刘华  邹叔骋  黄红星  张卫民  李创华  刘博  李凌 
单位:湖南省脑科医院 神经外科, 湖南 长沙 410007
关键词:辛伐他汀 caspase-7 c-IAP-1 脑出血 
分类号:R651
出版年·卷·期(页码):2019·47·第八期(925-930)
摘要:

目的:通过观察辛伐他汀对大鼠脑出血后脑组织中的半胱氨酸蛋白酶7(Caspase-7)和凋亡抑制蛋白1(c-IAP-1)的表达,探讨辛伐他汀可能的神经保护作用以及机制。方法:采用自体凝固血注入右侧尾状核法建立脑出血模型。将84只SD大鼠随机分组为假手术组Sham、脑出血组(ICH组)和辛伐他汀干预组(SIM组),每组28只。每组分别于术后12 h、24 h、72 h、5 d各取7只大鼠进行造模并实验。采用免疫组化法检测caspase-7和c-IAP-1阳性产物的分布情况。采用实时荧光定量PCR检测各组大鼠脑组织中caspase-7和c-IAP-1表达状况。结果:免疫组化法观察Sham组c-IAP-1和caspase-7阳性细胞均有表达,与ICH组和SIM组每个时间点相比较阳性细胞均显著增加。除脑出血后12 h外,其余各时间点SIM组要比ICH组caspase-7阳性细胞表达减少,c-IAP-1阳性细胞表达增加;实时荧光定量PCR法检测结果显示,Sham组与ICH、SIM组相比caspase-7和c-IAP-1表达水平低。在12 h ICH组和SIM组相比,caspase-7和c-IAP-1表达无显著性差异(P>0.05),其他时间点ICH组和SIM组相比,caspase-7表达上升,c-IAP-1表达降低,均有显著性差异(P<0.05)。结论:辛伐他汀能够降低脑出血后神经功能缺损症状以及抑制细胞凋亡,对神经功能起到一定的保护作用。

Objective:To investigate the possible neuroprotective effect and mechanism of simvastatin on the expression of cystein 7 (caspase-7) and apoptosis inhibitor protein 1 (c-IAP-1) in brain tissue of rats after intracerebral hemorrhage (ICH). Methods:An intracerebral hemorrhage model was established by injecting autologous coagulation blood into the right caudate nucleus. A total of 84 SD rats were randomly divided into Sham group (n=28), cerebral hemorrhage group (ICH group, n=28), and simvastatin intervention group (SIM group, 28). Seven rats in each group were used for modeling and experiment at 12 h, 24 h, 72 h and 5 d respectively. Immunohistochemistry was used to detect the distribution of caspase-7 and C-IAP-1 positive products. Real-time fluorescent quantitative PCR was used to detect the expression of caspase-7 and C-IAP-1 in brain tissue of each group.Results:The expression of C-IAP-1 and caspase-7 positive cells in Sham group was observed using mmunohistochemical method. Compared with ICH group and SIM group, the expression of C-IAP-1 and caspase-7 positive cells were significantly increased. The expression of caspase-7 positive cells and C-IAP-1 positive cells in SIM group were significantly lower than that in ICH group except 12 hours after intracerebral hemorrhage. The expression of caspase-7 and C-IAP-1 in Sham group was lower than that in ICH and SIM group. Compared with SIM group, the expression of caspase-7 and C-IAP-1 in ICH group was not significantly different at 12 hours (P>0.05). Compared with SIM group, the expression of caspase-7 and C-IAP-1 in ICH group increased and decreased at other time points (P<0.05).Conclusion:Simvastatin can reduce the neurological deficit after intracerebral hemorrhage, and inhibit cell apoptosis to protect nerve function.

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