瑞舒伐他汀预处理对大鼠脑缺血再灌注损伤的神经保护作用

Neuroprotective effects of rosuvastatin preconditioning on cerebral ischemia reperfusion injury in rats

目的观察瑞舒伐他汀预处理对大鼠脑缺血再灌注损伤的神经保护作用。方法 48只SD大鼠随机分为4组:假手术组、脑缺血再灌注组(I/R组),均正常喂养;溶剂对照组(用生理盐水)和瑞舒伐他汀预处理组(用瑞舒伐他汀5 mg·kg-1·d-1),均1次/天,连续灌胃10 d。用线栓法制作大鼠大脑中动脉局灶性I/R模型,于缺血2 h后再灌注24 h后行神经功能评分,断头取脑,制作病理切片。TUNEL染色法原位检测大鼠缺血半暗带区神经元细胞凋亡情况,免疫组织化学法检测caspase-3、caspase-9表达水平的变化。结果与I/R组和对照组相比,预处理组大鼠神经功能明显改善,缺血半暗带区神经元细胞凋亡程度明显减少,caspase-3和caspase-9表达均显著下调(均P<0.05)。结论瑞舒伐他汀预处理对大鼠脑缺血再灌注损伤有神经保护作用,其机制可能与抑制胞凋亡有关。

Objective To investigate the effects of rosuvastatin preconditioning on apoptosis and the apoptosis-related proteins in rats with focal cerebral ischemia-reperfusion.Methods Forty eight male adult Sprague-Dawley rats were randomly assigned into four groups ： Sham operation group（sham group）,focal cerebral ischemia-reperfusion group（I/R group）,vehicle adminerstration group（vehicle group）,and rosuvastatin preconditioning group（test group）.Before making a model,the rats in the test group were lavaged with rosuvastatin 5 mg.kg^-1.d^-1,once a day for 10 consecutive days,and the same volume of normal saline was lavaged in the vehicle group.The middle cerebral artery occlusion reperfusion model was made by the suture method（ischemia for 2 hours,and reperfusion for 24 hours）.After that,the animals were neurologically assessed on a 5 point scale.Rats were sacrificed by decapitation.TUNEL staining was used to observe neuron apopotosis.The level of caspase-3 and caspase-9 expression were measured by immunohistochemical.Results Compared with I/R group and vehicle group,neurological functions were better in test group,TUNEL positive cells and caspase-3,caspase-9 immunoreative neurons in the rats of test group were downregulated（P〈 0.05）.Conclusion Rosuvastatin can suppress neurocyte apoptosis in cerebral ischemia,whose mechanisms seemed related to inhibiting the expression of caspase-3 and caspase-9.