雷帕霉素对大鼠脑缺血再灌注后神经元损害的保护作用  

Protective effects of rapamycin on neuronal damage after focal cerebral ischemia and reperfusion in rats

作　　者：李丽茹[1] 黄杰[2] Li Liru;Huang Jie(Emergency Medical Department, the Sixth People＇s Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai Fengxian District Central Hospital, Shanghai 201400, China;Department of Intergrated Tradition and Western Medicine, the Sixth People＇s Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai Fengxian District Central Hospital, Shanghai 201400, China)

机构地区：[1]上海交通大学附属第六人民医院南院 上海市奉贤区中心医院急诊医学科,201400 [2]上海交通大学附属第六人民医院南院 上海市奉贤区中心医院中西医结合科,201400

出　　处：《神经疾病与精神卫生》2018年第3期183-186,F0003,共5页Journal of Neuroscience and Mental Health

基　　金：上海市奉贤区科学技术委员会科学技术发展基金项目（奉科20131407）;上海市卫生局面上项目（20124286）

摘　　要：目的观察雷帕霉素对大鼠脑缺血再灌注后神经元损害的保护作用。方法52只雄性sD大鼠随机分为对照组和实验组（雷帕霉素干预）各24只，另4只为假手术组。采用Longa线栓法制备大鼠局灶性脑缺血再灌注模型，缺血3h后，于再灌注4h、6h、12h、24h、72h、7d进行各指标观察；其中实验组在构建脑梗模型之前进行腹腔注射雷帕霉素（1mg／kg），假手术组不插线，其余过程同对照组。采用TFC染色法观察脑组织变化；免疫组织化学（免疫荧光法）检测Bcl-2、Caspase-3及自噬相关蛋白LC-3的变化。结果TTC染色假手术组未见缺血表现，缺血3h后可见病灶侧脑组织苍白，实验组病灶小于对照组。实验组大鼠灌注6、12、24h时神经功能缺损评分均明显低于对照组（P〈0．05）。Caspase-3的表达：再灌注4h表达显著增高，至24h左右达高峰，实验组再灌注6h、24h、7d表达明显低于对照组，差异有统计学意义（P〈0．05）；Bcl-2的表达：再灌注4h增多，24h达高峰，实验组再灌注4、6、12、24h表达明显高于对照组（P〈0．05）；实验组LC-3表达明显高于对照组。结论雷帕霉素能促进LC-3表达，抑制细胞凋亡；抑制Caspase-3的表达，增加Bcl-2的表达从而减轻缺血所致的损伤，对大鼠缺血后神经功能的恢复有确切的疗效。Objective To observe and evaluate the protective effects of rapamycin on neuronal damage after focal cerebral ischemia-reperfusion in rats. Methods A total of 52 male SD rats were randomly divided into control group and experimental group （rapamycin intervention group）, with 24 rats in each group, and the other 4 rats were assigned into sham-operated group. The model of focal ischemia-reperfusion was prepared by Longa＇s method. Each index was observed at the 4th, 6th, 12th, 24th, 72nd hour and the 7th day after reperfusion for 3 hours. The experimental group was injected with rapamycin （1 mg/kg） intraperitoneally before establishing the cerebral infarction model. The sham-operated group did not plug the thread, and the rest of the process was same with the control group. The changes of brain tissue were observed by TTC staining. Changes of Bcl-2, Caspase-3 and autophagy related prtein LC-3 were detected by immunohistochemistry （immunofluorescence）. Results There was no ischemia detection in TTC staining sham operation. After 3 hours of ischemia, the lesion side brain tissue was pale, and the lesions in the experimental group were smaller than those in the control group. The score of neurological deficit of the experimental group at the 6th, 12th and 24th hour after reperfusion was lower than that of the control group （P 〈0.05）. The expression of caspase-3 increased significantly at the 4th hour after reperfusion and peaked at 24h, and the expression of caspase-3 of experimental group at the 6th, 24th hour and the 7th day was significantly lower than that of control group, and the difference was statistically significant （P 〈 0.05）. The expression of Bcl-2 increased at the 4th hour after repeffusion, and peaked at the 24th hour after reperfusion. The reperfusion at the 4th, 6th, 12th and 24th hour of the experimental group was significantly higher than that of the control group （P 〈 0.05）. The expression of LC-3 of the experimental group was significantly higher than that of the con

关 键 词：雷帕霉素 脑缺血 再灌注 BCL-2 CASPASE-3 

分 类 号：R743.33[医药卫生—神经病学与精神病学]