辛伐他汀对局灶性脑缺血大鼠半暗带区缓激肽受体mRNA表达的影响

Effects of Simvastatin on the Expression of Bradykinin Receptors mRNA in Penumbra after Focal Cerebral Ischemia-reperfusion in Rats

目的:探讨辛伐他汀预处理对局灶性脑缺血大鼠半暗带缓激肽受体基因表达的影响。方法:72只雄性SD大鼠随机分为3组:辛伐他汀干预组(干预组,给予辛伐他汀10 mg.kg-1.d-1和生理盐水1 mL的悬浊液灌胃),脑缺血再灌注模型组(模型组,给予等体积生理盐水灌胃),假手术组(给予等体积生理盐水灌胃),3组分别预处理14 d。参照Longa法将干预组和模型组建立大脑中动脉栓塞模型,假手术组仅暴露右侧颈总和颈内动脉主干,不栓塞。并将各组随机分为再灌注3、24和48 h 3个亚组(均n=8)。于对应时间点行神经功能评分,用苏木精-伊红染色检测脑组织形态学,荧光定量RT-PCR技术检测脑缺血半暗带缓激肽B1、B2受体(BK-1Rs、BK-2Rs)的基因表达水平。结果:与模型组相比,3、24和48 h干预组大鼠缺血再灌注后神经功能改善、功能评分值降低(分别P<0.05,P<0.05,P<0.01),脑组织病理形态学变化减轻。荧光定量RT-PCR检测发现,3 h模型组脑缺血半暗带BK-1Rs、BK-2Rs与假手术组比表达减低,差异有统计学意义(P<0.05,P<0.01);3 h干预组BK-1Rs、BK-2Rs与模型组比表达增加,差异有统计学意义(P<0.01,P<0.05),24和48 h模型组脑缺血半暗带BK-1Rs与假手术组比表达减低,差异有统计学意义(P<0.01,P<0.01);24和48 h干预组BK-1Rs与模型组比表达增加,差异有统计学意义(P<0.01,P<0.01)。结论:辛伐他汀预处理可改善大鼠局灶性脑缺血再灌注神经功能缺损及组织病理形态学,其机制可能与增加脑缺血半暗带BK-1Rs、BK-2Rs的表达有关。

Aim： To determine the effects of simvastatin on the expression of bradykinin receptors in penumbra after focal cerebral ischemia/reperfusion in rats.Methods： 72 male SD rats were randomly divided into three groups,sham-operation group,cerebral ischemia-reperfusion group（0.9% saline）,simvastatin preconditioning group（10 mg.kg-1.d-1）,which received pretreatment 14 days respectively.The model of middle cerebral artery occlusion（MCAO） was established according to the method reported by Longa except shamoperation group.Each group was further divided into three subgroups at 3 h,24 h and 48 h after reperfusion,and each subgroup consisted of eight rats.Among there subgroups,at 3 h,24 h and 48 h after reperfusion,the animals were observed for neurological deficits and the morphology of brain tissue by neurological function score and HE staining,the levers of mRNA of BK-1Rs and BK-2Rs were detected by fluorescent quantitative RT-PCR.Results： Compared with the ischemia-reperfusion group,the neurological function of simvastatin preconditioning group was significantly improved and its neurological function scores（P0.05,P0.05,P0.01） decreased at 3 h,24 h,48 h,and the changes of pathological damages became small.Compared with the sham-operation group,fluorescent quantitative RT-PCR analysis showed that the mRNA levels of BK1Rs and BK-2Rs in ischemia penumbra significantly decreased in 3 h ischemia-reperfusion group（P0.05,P0.01）.Compared with the ischemia-reperfusion group,the mRNA levels of BK-1Rs and BK-2Rs in ischemia penumbra significantly increased in 3 h preconditioning group（P0.01,P0.05）.Compared with the shamoperation group,the mRNA levels of BK-1Rs in ischemia penumbra significantly decreased in 24 h and 48h ischemia-reperfusion group（P0.01,P0.01）.Compared with the ischemia-reperfusion group,the mRNA levels of BK-1Rs in ischemia penumbra significantly increased in 24 h and 48 h preconditioning group（P0.01,P0.01）.Conclusion： Pretreatment with simvastatin before cerebral ischemia /reperfusion injury in rats can reduce the neurological deficits and improve brain tissue pathomorphology.This beneficial effects of simvastatin may be partly mediated by an increased expression of BK-1Rs and BK-2Rs in the ischemia penumbra.