目的：观察二苯乙烯苷(tetrahydroxystilbene glucoside,TSG)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)拟帕金森病(Parkinson's disease,PD)模型小鼠行为学及多巴胺能神经元的影响。方法 C57BL小鼠按数字表法随机分为对照组、模型组、TSG 小剂量组(TSG 60 mg/ kg)和 TSG 大剂量组(TSG 120 mg/ kg)。 MPTP 30 mg/ kg 腹腔注射5 d 建立拟 PD 小鼠模型。采用爬杆实验、转棒实验和自主活动实验测试小鼠行为学变化。免疫组织化学法检测各组小鼠黑质处酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞的表达情况。高效液相色谱电化学检测法测定小鼠纹状体内多巴胺及其代谢产物的含量。结果与对照组相比,MPTP 模型组小鼠爬杆时间显著延长,在转棒上的停留时间明显缩短,自主活动数减少,脑黑质处 TH 阳性细胞数量显著减少,纹状体内多巴胺及其代谢产物含量显著降低。与模型组小鼠相比,TSG 用药组小鼠运动协调性显著增强,脑黑质处 TH 阳性细胞数量增加,纹状体内多巴胺含量升高。结论 TSG 可改善 MPTP 模型小鼠的行为学,保护黑质多巴胺能神经元。 TSG 可能具有潜在的防治 PD 的作用。
Objective To observe effects of tetrahydroxystilbene glucoside ( TSG) on behavior and content of dopamine and its metabolites in striatum of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) model mice. Methods Mice were randomly divided into normal control group, model group, and TSG low dose(60 mg/ kg) and high dose(120 mg/ kg) groups. The behavior changes of mice were observed by pole test, Rotarod test and spontaneous movement test. The tyrosine hydroxylase(TH) positive cells were detected by immunohistochemical method. The content of dopamine(DA) and its metabolic products in striatum were determined by HPLC-ECD. Results MPTP model mice showed behavior deficit. The counts of TH positive neurons in substantia nigra and the content of dopamine and its metabolites in striatum in model mice decreased significantly compared with control group. TSG ameliorated the behavior deficits, increased the number of TH positive neurons in the substantia nigra, and elevated the content of dopamine in striatum compared with model mice. Conclusion TSG protected dopaminergic neurons against MPTP-induced damage, and may become a candidate drug for prevention and treatment of Parkinson's disease.