辛伐他汀预处理对大鼠局灶性脑缺血不同灌注时间窗脑损伤的保护作用及机制研究

Protective effect of simvastatin pretreatment on focal cerebral ischemia/reperfusion injury at different reperfusion time in rats

目的研究辛伐他汀(simvastatin)预处理对不同灌注时间窗脑损伤预防性脑保护作用及机制;探讨通过辛伐他汀预处理延长再灌注时间窗的可行性。方法线栓法制作大鼠缺血再灌注损伤模型,实验动物随机分为4组:A组为假手术组;B组为缺血/再灌注组;C组为缺血/再灌注组+辛伐他汀组;D组为缺血/再灌注组+辛伐他汀+L-NAME组。B、C、D组又各分为再灌注后2、46、h组。各组在相应时间点进行神经功能评分,测梗死体积,测定脑组织超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)活性以及丙二醛(MDA)含量。结果C组各时间点的神经功能评分、梗死体积小于B组(P<0.05);C组各时间点MDA含量、MPO活性均低于B组(P<0.05及P<0.01),而SOD活性高于B组(P<0.05及P<0.01);D组各时间点相应指标与B组无显著性差异(P>0.05)。结论辛伐他汀预处理可改善神经功能评分,缩小梗死体积,其发生机制可能与增加eNOS合成,提高脑组织抗炎、抗氧化能力有关。

Objective To study the protection of simvastatin pretreatment on focal cerebra/ischemia/repezfusion injury and the possibility of extending the reperfusion time window in rats. Methods Sprague- Dawley rats were randomly divided into four groups, which, except for the sham control groulp, were respectively pretreated with saline, simvastatin and simvastatin plus L- NAME. The MCAO （middle cerebral artery occlusion） was continued for varied periods of time （2 h, 4 h and 6 h）. The neurological findings were scored 24 hours after MCAO. The brain was then removed from the skull; coronal sections were cut and stained with Trc to locate and measure the region of infarct. The cerebral cortex was separated to assess the activities of SOD and MPO and the content of MDA, Results Compared with group B, the behavior score and infarct volume in group C were reduced remarkably （ P 〈 0.05） ; the activity of MPO and the content of MDA were lower in group C than those in group B （ P 〈 0.01 and P 〈 0.05） ; the activity of SOD was higher in group C than that in group B （ P 〈 0.01 or P 〈 0.05）, No differences were found in those items between group B and D （ P 〉 0.05）, Conclusion Pretreatment with simvastatin provides potent neuroprotection on ischemic/reperfusion injury. The NO derived from eNOS may play a key role in the neuroprotection of simvastafin,