中文摘要：

目的：观察1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病小鼠模型的行为学及组织学变化。方法：C57/BL小鼠腹腔注射MPTP 25 mg/kg,每周2次,连续5周。通过旷场实验和强迫游泳实验检测小鼠的行为变化,分别使用抗酪氨酸羟化酶（TH）单克隆抗体和抗诱生型一氧化氮合酶（iN0S）单克隆抗体、抗精氨酸酶I（Arg1）多克隆抗体作为多巴胺能神经元和小胶质细胞M1、M2两种极化表型的分子标志进行免疫荧光染色。结果：旷场实验中,模型组小鼠的活动总路程较对照组小鼠有减少趋势,但无明显统计学差异（P〉0.05）,而其中央活动时间较正常对照组明显缩短（P〈0.05）;强迫游泳实验中,模型组小鼠在水中的不动时间较对照组显著延长（P〈0.05）。与对照组相比,模型组小鼠中脑黑质致密部TH阳性神经细胞数目减少约87%,两组TH阳性神经细胞计数比较差异显著（P〈0.01）。模型组iNOS所染M1型小胶质细胞数量较对照组增加约54%,有显著性差异（P〈0.05）,而Arg1标志的M2型细胞数量,虽较对照组有减少趋势,但无明显统计学差异（P〉0.05）。结论：MPTP所致的C57/BL小鼠行为学及神经病理学改变与临床PD患者类似,脑内黑质区小胶质细胞两种极化表型混合存在,但M1型极化较正常有所改变,M2型变化不明显。

英文摘要：

Objective： To observe the changes of ethology and histopathology in the mice model of Parkinson＇s Disease induced by 1-methyl-4-phenyl-1,2,3,6-tetraydropyridine （MPTP）. Methods： The chronically PD models were established with intraperitoneal injections of MPTP in C57/BL mice, 25 mg/kg, 2times/week for 5 weeks. The effects of MPTP on the behavior were tested by open-field and forced swim test; the number ofdopamine （DA） neurons and M1/M2 polarized microglial cells were analyzed by immunofiuorescence staining of anti-tyrosine hydroxylase （TH） monoclonal antibody, and two types ofmicroglial polarization molecular mark Anti-Inducible nitric oxide synthase （iNOS） antibody and Anti-liver Arginase（Argl）antibody in brain frozen sections. Results： In the open-field test, the total distance of the model mice showed decreasing trend compared with that of the control group, but no statistically significant differen- ce （P〉0.05）. However, the central activity time was significantly shorter than that of the control group （P〈0.05）. The immobility time of model mice was obviously longer （P〈0.05） than that of the control group in the forced swimming test. Compared with the control group, the number of TH-positive neurons in the brain SNc of model group mice decreased to approximately 87% of that of the control group, with statistical significance （P〈0.01）. In the model group, the number of iNOS positive M1 microglia increased approximately 54% of that of the control group, with statistical significance （P〈0.05）, and the number of M2 microglia marked by Argl was less than the control group, but no significant difference （P〉 0.05）. Conclusion： The change of ethology and histopathology induced by MPTP in C57/BL mice were similar with PD patients. The M1 and M2 polarization phenotypes of Microglia are both present in the brain SNc of MPTP induced PD mice model, and M1 polarization was augmented compared with normal control, however, the variation of M2 type was not obv