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目的研究绿茶多酚的主要单体成分表没食子儿茶素没食子酸酯(EGCG)的多巴胺能神经元保护作用。方法利用1-甲基-4-苯基-1,2,3,6-四羟吡啶(MPTP)及其代谢产物1-甲基-4-苯基吡啶(MPP+)分别造成选择性多巴胺能神经元损伤动物模型和细胞模型,给予不同剂量EGCG,免疫组织化学染色方法标记酪氨酸羟化酶(TH)阳性细胞作为多巴胺能神经元标志,通过体视学方法观察不同剂量EGCG对阳性细胞数目的影响,同时利用膜抗原CD11b标记小胶质细胞,观察EGCG对小胶质细胞激活的作用。结果在MPP+诱导的原代培养中脑腹侧多巴胺能神经元损伤模型中, 预先给予EGCG 1μmol／L-100μmol／L可显著减轻MPP+诱导的多巴胺能神经元减少,保护率为22．2％～80．5％。在体情况下,1 mg／kg剂量EGCG腹腔注射对MPTP模型小鼠A9区TH免疫阳性细胞丢失的保护率为71．7％,对中脑区域总TH免疫阳性细胞数丢失的保护率为50．9％,5 mg／kg和10 mg／kg剂量组中脑各区域TH阳性神经元数量均较模型组高(P<0．05),同时,EGCG对MPTP所致的中脑部位小胶质细胞的激活具有抑制效应。结论本研究结果提示EGCG 在一定剂量范围内对多巴胺能神经元具有显著的保护作用,具有潜在治疗帕金森病的价值,EGCG对多巴胺能神经元的在体保护作用可能与其抑制小胶质细胞的激活密切相关。
Objective To study the protective effect of epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, on dopaminergic neurons. Methods The selective dopaminergic neurons were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridine The animal model and cell model were induced by different doses of EGCG. The tyrosine hydroxylase (TH) -positive cells were labeled by immunohistochemistry as markers of dopaminergic neurons. The number of positive cells of EGCG was observed by stereological methods Meanwhile, microglia were labeled with membrane antigen CD11b to observe the effect of EGCG on microglia activation. Results In MPP + -induced primary ventricle model of dopaminergic neuron injury in the ventral dopaminergic neurons, pretreatment with EGCG 1μmol / L-100μmol / L significantly reduced the decrease of dopaminergic neurons induced by MPP +, with a protective rate of 22.2% 80.5%. In vivo, the protective rate of intracerebroventricular injection of EGCG at a dose of 1 mg / kg on TH-immunoreactive cells in the A9 region of MPTP mice was 71.7%, and that of the TH-immunoreactive cells in the midbrain region was 50% .9%, 5 mg / kg and 10 mg / kg dose group, the number of TH positive neurons in each region was higher than that in the model group (P <0.05); meanwhile, Glial activation has a suppressive effect. Conclusions The results of this study suggest that EGCG has a significant protective effect on dopaminergic neurons in a certain dose range and has potential value in the treatment of Parkinson’s disease. The protective effect of EGCG on dopaminergic neurons may be related to its inhibitory effect on microglial cells Activation is closely related.