吗啡成瘾时脑内Fas、Bcl-2和Caspase-3蛋白表达的改变  

Changes of Fas,Bcl-2 and Caspase-3 protein in rat brain during morphine addiction

作　　者：刘立伟[1] 王新华[2] 傅舒昆[1] 吴青华[3] 傅强[4] 

机构地区：[1]同济大学附属第十人民医院麻醉科,上海200072 [2]同济大学附属东方医院麻醉科,上海200120 [3]解放军第150医院麻醉科,洛阳471031 [4]解放军总医院麻醉科,北京100853

出　　处：《第二军医大学学报》2012年第10期1086-1089,共4页Academic Journal of Second Military Medical University

摘　　要：目的观察吗啡成瘾时脑细胞中凋亡相关蛋白Fas、Caspase-3和Bcl-2表达的改变。方法将48只体质量为190～210g的成年SD大鼠随机分为3组:吗啡依赖组、吗啡戒断组和对照组,每组16只。依据药物递增原则,依赖组和戒断组大鼠腹腔内给予吗啡13d,建立吗啡成瘾模型。戒断组大鼠在成瘾后腹腔内注射纳洛酮5mg/kg,诱导戒断30min。对照组大鼠在相同的治疗时间腹腔内注射生理盐水。应用免疫组织化学、蛋白印迹分析方法检测大鼠海马区Fas、Bcl-2和Caspase-3蛋白的表达。结果与对照组比较,吗啡依赖组和戒断组大鼠海马区Fas和Caspase-3的表达增加(P<0.01),而Bcl-2的表达降低(P<0.01)。结论长期应用吗啡可通过Fas、Caspase-3表达的增加和Bcl-2表达的降低诱发脑细胞异常凋亡,这可能是阿片类药物引起神经损害的机制之一。Objective To investigate the changes of apoptosis-related proteins Fas,Caspase-3 and Bcl-2 expression in rat brain during morphine addiction. Methods A total of 48 adult male Sprague-Dawley rats,weighing 190-210 g,were randomly divided into 3 groups （n=16）： chronic morphine-dependent group,chronic morphine-abstinent group and control group.The rats in dependent group and abstinent group were chronically treated with morphine for 13 days to establish morphine dependent model.In the abstinent group,the withdrawal syndromes were induced with intraperitoneal injection of naloxone 5 mg/kg for 30 min.The control group was injected with normal saline.Immunohistochemistry and Western blotting analysis were used to examine the expression of Fas,Bcl-2 and Caspase-3 proteins. Results Compared with the control group,the other two groups had significantly increased expression of Fas and Caspase-3（P〈0.01） and significantly decreased expresssion of Bcl-2（P〈0.01） in the hippocampal synapse. Conclusion It is demonstrated that long term use of morphine can promote abnormal neuronal apoptosis in rat brain by enhancing the expression of pro-apoptotic Fas,Caspase-3 and decreasing the expression of anti-apoptotic Bcl-2,which might be one of the mechanisms for opiate-induced neuronal damage.

关 键 词：吗啡依赖 海马 细胞凋亡 FAS BCL-2 Caspase-3 

分 类 号：R749.61[医药卫生—神经病学与精神病学]