阿托伐他汀预处理对大鼠脑缺血再灌注损伤Caspase-3、Bcl-2表达的影响

[目的]探讨阿托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:对照组、假手术组、缺血再灌注组和阿托伐他汀预处理组.阿托伐他汀预处理组在模型制备前用阿托伐他汀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.以线拴法制作大鼠大脑中动脉缺血再灌注模型,于缺血2h再灌注24 h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、凋亡细胞数及半胱氨酸天冬氨酸蛋白酶-3 (Caspase-3)、B细胞淋巴瘤/白血病-2基因(Bcl-2)表达.[结果]与对照组和假手术组比较,缺血再灌注组和阿托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,Caspase-3、Bcl-2表达显著增加(P＜0.01).与缺血再灌注组相比,阿托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Caspase-3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]阿托伐他汀预处理对大鼠脑缺血再灌注有神经保护作用,其作用机制可能与阿托伐他汀上调脑组织中Bcl-2、下调Caspase-3表达,抑制细胞凋亡有关.

Effects of atorvastatin preconditioning on the expressions of Caspase-3 and Bcl-2 in rats with focal cerebral ischemia reperfusion

[Objective] To explore the protective effect of atorvastatin 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 control group, sham operation group, focal cerebral ischemia reperfusion group （FCIR） and atorvastatin preconditioning group （SS preconditioning）. Before making a model, the rats in the SS preconditioning group were lavaged with atorvastatin 20 mg/kg, once a day for 10 consecutive days, and the same volume of the normal saline was lavaged for 10 consecutive days, in the sham operation and the FCIR groups. Middle cerebral artery occlusion reperfusion model was made by ligation decapitated method（ischemia for 2 hours, and reperfusion for 4 hours）. After that, the animals were neurologically assessed on a 5 point scale, and then. The volume of infarction was measured by TI＇C staining, the expressions of Caspase-3 and Bcl-2 were detected by immunohistochemistry, and the number of neuron apoptosis was detected by TUNEL. [Results] Compared with the control and sham groups, the infarction volume enlarged, the expressions of Caspasa-3 and Bcl-2 and the number of neuron apoptosis increased in the FCIR and the SS preconditioning groups（P〈0,01 ）.Compared with the FCIR group, the volume of infarction was significantly reduced （P〈0.01）, the neurological scores were improved （P〈0.05）, the expression of Caspase-3 and the number of neuron apoptosis was significantly decreased（P〈0.05, P〈0.01 ）, the expression of Bcl-2 was significantly increasedin SS preconditioning group （P〈0.05）. [Conclusion ] The results suggested that simvastatin plays a protective role in focal cerebral ischemia reperfusion. The mechanism might be related to the increase in protein expression of Bcl-2 and the decrease in protein expression of Caspase-3, and the restrain of apoptosis.