辛伐他汀预处理对脑缺血再灌注损伤Bcl-2和Bax表达的影响

Effects of simvastatin preconditioning on expression of Bcl-2 and Bax in rats with focal cerebral ischemia reperfusion

目的:探讨辛伐他汀预处理对大鼠局灶性脑缺血再灌注损伤的保护作用及其机制。方法:随机将48只雄性SD大鼠分为4组:空白对照组、假手术组、缺血再灌注组和辛伐他汀预处理组。辛伐他汀预处理组在模型制备前用辛伐他汀20mg/kg连续灌胃10d,1次/d;假手术组及缺血再灌注组用相同体积的等渗盐水连续灌胃10d。以线栓法制作大鼠大脑中动脉缺血再灌注模型,于缺血2h再灌注24h后行5分制神经功能评分,并断头取脑分别测定脑梗死体积、凋亡细胞数及Bcl-2、Bax表达。结果:与空白对照组和假手术组比较,缺血再灌注组和辛伐他汀预处理组神经功能缺损较为严重,脑梗死体积增大,凋亡细胞数目增多,Bcl-2、Bax表达增加(均P<0.01)。与缺血再灌注组相比,辛伐他汀预处理组神经功能有不同程度改善,脑梗死体积明显减小,凋亡细胞数及Bax表达降低,Bcl-2表达增高,比较差异均有统计学意义(P<0.05,P<0.01)。结论:辛伐他汀预处理对大鼠脑缺血再灌注有神经保护作用,其作用机制可能与辛伐他汀上调脑组织中Bcl-2、下调Bax表达,抑制细胞凋亡有关。

Objective：To explore neuroprotective effect of simvastatin preconditioning on cerebral ischemia reperfusion injury in Sprague-Dawley rats and its mechanism.Methods：forty-eight adult healthy male SD rats were randomly divided into the control group,sham operation group,Focal Cerebral Ischemia Reperfusion group（FCIR）,simvastatin preconditioning group（SS preconditioning）.Before making a model,the rats in the simvastatin preconditioning group were lavaged with simvastatin 20 mg/kg,once a day for 10 consecutive days,and the same volume of normal saline was lavaged for 10 consecutive days in the sham operation and FCIR groups.The middle cerebral artery occlusion reperfusion model was made by the suture method（ischemia for 2 hours,and reperfusion for 4 hours）.After that,the animals were neurologically assessed on a 5 point scale,and then beheaded.The volume of infarction were measured by TTC staining,the expressionof Bcl-2 and Bax were detected by immunohistochemistry,and the number of the neuron apoptosis wasdetected by TUNEL.Results：Compared with the control and sham groups,the infarction volume enlarged,the expression of Bcl-2 and Bax and the number of nueron apoptosis increased in the FCIR and SS preconditioning groups（P〈0.01）.Compared with the FCIR group,the volume of infarction significantly reduced in SS preconditioning group（P〈0.01）,the neurological scores were improved（P〈0.05）,the expression of Bax and the number of neuron apoptosis was significantly decreased（P〈0.05,P〈0.01）,the expression of Bcl-2 was significantly increased（P〈0.05）.Conclusion：The results suggested that simvastatin p layed a role of neuroprotection in focal cerebral ischemia reperfusion.The mechanism might be related to the increase of Bcl-2 and the decrease of Bax protein expression and the number of TUNEL positive cells.