甲基苯丙胺对大鼠纹状体小胶质细胞及NOS的影响

Effect of methamphetamine on the microglial cells and activity of nitric oxide synthases in rat striatum

目的观察甲基苯丙胺(METH)对大鼠纹状体内小胶质细胞的影响以及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)和结构性一氧化氮合酶(cNOS)的变化以及相互间的关系。方法建立METH给药模型,实验组给予METH,对照组给予等体积生理盐水,采用OX-42免疫组化观察小胶质细胞的变化情况,采用酶化学方法测量纹状体内的NOS、iNOS和cNOS的活性改变。结果与对照组相比,实验组纹状体区小胶质被细胞激活,数量显著增加(P<0.01),呈现为"灌木丛"(bushy)甚至"阿米巴样"(amoeboid),同时NOS、iNOS和cNOS的活性均显著升高(P<0.01)。结论小胶质细胞被激活,NOS活性升高,可能是METH引起中枢神经损伤的重要机制。

Objective To study the changes in the microglial cells and the activity of nitric oxide synthase （NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the striatum of rats with methamphetamine （METH） treatment. Methods The rats were randomly divided into two groups for injections with METH or saline. Specific antibody against OX-42 was used to detect the changes in the morphology and the number of microglia, and the activities of NOS, iNOS and cNOS were compared between the two groups. Results The microglial cells were activated and their number significantly increased in the striatum of rats with METH treatment as compared with those in the saline group. The activated microglial cells showed bushy and amoeboid morphologies in the METH group. METH also significantly enhanced the activities ofNOS, iNOS and cNOS in the striaturn （P〈0.05）. Conclusion Microglial activation and increased NOS activity may participate in METH-induced neurutoxity in rat striatum.