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

Effect of the simvastatin on the expression of caspase-7 and C-IAP-1 after intracerebral hemorrhage in rats

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.