吗啡成瘾时脑内Fas、Bcl-2和Caspase-3蛋白表达的改变
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国家自然科学基金


Changes of Fas, Bcl-2 and Caspase-3 protein in rat brain during morphine addiction
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    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190~210 g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13 d,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5 mg/kg,诱导戒断30 min。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。

    Abstract:

    ObjectiveTo investigate the changes of apoptosis-related proteins Fas,Caspase-3 and Bcl-2 expression in rat brain during morphine addiction. MethodsA 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. ResultsCompared 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. ConclusionIt 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.

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  • 收稿日期:2012-05-24
  • 最后修改日期:2012-07-10
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  • 在线发布日期: 2012-10-24
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