甲基苯丙胺中毒大鼠纹状体小胶质细胞的激活特性

目的研究甲基苯丙胺（methamphetamine,MA）中毒动物模型纹状体内小胶质细胞（microglia,MG）的激活特性。方法SPF级雄性Wistar大鼠,随机分为对照组和实验组,每组24只。实验组采取腹腔注射MA（15 mg/kg×8次,每次间隔12 h）;对照组按上述给药方式每次注射等量的生理盐水。两组分别于首次注射后第0.5、1、2、3、4、5、6和7天共8个时间点纹状体取材,进行CD-11b抗体免疫组化染色和超微结构观察形态学变化,另对免疫组化染色结果进行细胞激活率计算,并进行统计。结果光、电镜下,各时间点对照组的MG胞体瘦小、突起细长,呈＂细分枝状＂,胞核浓缩,胞质内细胞器稀少;实验组MG胞体变大、突起变短或消失,呈＂灌木丛状＂或＂阿米巴状＂,胞核电子密度降低,胞质内细胞器丰富。对照组各时间点MG的激活率维持在0.15水平以下,且随着观察时间的延长无明显变化趋势;而实验组MG的激活率与对照组相比,第1～7天均显著升高（P〈0.001）。结论MA的刺激可导致MG明显激活。

The Microglia Activation Characteristics of MA-induced Neurotoxicity in the Rats Striatum

Objective To investigate the activation characteristics of microglia（MG） in the rats striatum with MA-induced neurotoxicity. Methods Male Wistar rats were divided randomly into control group （n=24） and experimental group （n=24）. The rats of experimental group were injected intraperitoneally with MA （15 mg/kg×8 injections, at 12 hours interval）. The rats of control group were administrated with saline. The tissues of striatum of two rat groups were harvested at 0.5d, 1d, 2d, 3d, 4d, 5d, 6d and 7d post initial administrations of MA or saline. The structure changes were observed by transmission electron microscopy and CD-11b immunohistochemistry. The ratio of activated MG was calculated and statistically analyzed. Results In the control group, the morphological characteristics of the MG showed that the cell bodies were small with slender processes, high electronic density nucleus, and fewer organelles known as the ＂fork-type＂. In contrast, the MG in the MA-induced neurotoxicity group displayed larger cell body, shorter cell processes or disappeared, lower electronic density nucleus and rich organelles, resembling ＂bush-like＂ or ＂amoeba-like＂. The ratio of activated MG in control group was below 0.15 at all timepoints, whereas in the experimental group, the ratio of activated MG increased significantly from day 1 to day 7（P〈0.001 ）. Conclusion The continuous MA stimulation of the CNS results in prominent MG activation.