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目的：探讨MA 中毒多巴胺能神经毒性的损伤机制。方法：将Wistar 大鼠40 只，随机分成对照组10 只和实验组30 只(实验组分成三个亚组，分为末次给药后1 天组、4 天组和7 天组，n=10)。实验组给予20mg/kg 的MA 腹腔注射，对照组给予同样剂量的生理盐水，每天注射一次，注射时间为20：00，连续注射4 天。分别于末次给药后1 天，7 天，14 天处死实验大鼠，用免疫组织化学染色法（S-P 法）和荧光分光光度计法检测大鼠中脑黑质致密区（SNC）、中脑腹侧被盖区(VTA)、前额叶皮质（PFC）以及纹状体（CPu）四个脑区的多巴胺神经元细胞的形态和数量的变化，对神经纤维进行灰度值分析。结果：1、黑质致密区和腹侧被盖区TH 阳性细胞图像分析结果与细胞计数分析结果一致：与对照组相比，各实验组TH 免疫反应阳性降低，差异具显著性（P<0.05），d1 组开始降低（P<0.05），d7 组达到低谷（P<0.01），d14 天组黑质致密区和腹侧被盖区TH 免疫反应阳性有不同程度的恢复（P<0.05）。2、纹状体和前额叶皮质TH 阳性纤维图像定量分析结果：各实验组TH 免疫反应阳性均减低（P<0.05），d7 组阳性反应最弱（P<0. 01），d14 组仍未恢复（P<0.05）。3、黑质致密区、腹侧被盖区、纹状体及前额叶皮质荧光分光光度计检测DA 递质含量结果：与上述免疫组化结果基本一致。结论：1、大鼠各脑区TH 阳性表达和DA 含量，均出现不同程度的减低。2、MA 中毒大鼠各脑区DA 递质含量的变化与TH 的变化结果基本一致。

英文摘要:

Objective: To investgate injury mechanism of methamphetamine dopaminergic toxicity. Methods: 40 male rats were randomly divided into control group (n=10) and experimental group (dividing it into the first, fourth and seventh group after the last injection, n=10).Rats in the experimental group were intraperitoneal injected with MA(20mg/kg ,8 pm, ip ×4 d), and those in the control group were injected with saline with the same volume (20 mg·kg-1 ,8 pm, ip ×4 d ).Through S-P TH antibody and spectrophotofluorometer in DA, the mentioned seven brain regions were examined, including SNC.VTA.PFC and CPu. The mentioned TH masculine cell and neurotic fibre were analysed by the image analysis system. Results: 1.The image analysing results was similar to the results of cell counting in the SNC and VTA TH masculine cell: Compared with relation group, TH immunity reaction masculine in the different experimental group reduces with obvious difference (P<0.05), d1 begins to reduce (P<0.05), d7 gets to the lowest level, (P<0.01) d14 SNC and VTA masculine cell regains to different degree (P<0.05).2.The analysing results of TH masculine Neurotic Fibre Density in the PFC and CPu：Compared with relation group, The changes of TH masculine Neurotic Fibre Density reduces with obvious difference, d1 begins to reduce, d7 gets to the lowest level, d14 masculine cell regains to different degree (P＞0.05).3. The results of analysing DA by SPF rat methamphetamine intoxication SNC. VTA and CPu: It is similar to the analysing results of the SNC. VTA . PFC and CPu TH immunohistochemistry results in five brain regions. Conclusion: 1. To different degrees, the reduction and changes appear in rat SNC、VTA、PFC and CPu, with dose dependent. 2. The changes of TH were consistent with rat methamphetamine intoxication and DA transmitter.

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