全反式维甲酸通过增强调节性T细胞的抑炎效应发挥对多巴胺能神经元的保护作用

目的探讨全反式维甲酸(ATRA)对帕金森病(PD)小鼠多巴胺能神经元的作用及其机制。方法将野生型小鼠随机分为MPTP对照组与ATRA+MPTP组,造模前后进行行为学检测,流式细胞学技术检测外周T淋巴细胞亚群,实时定量PCR法检测脉络丛黏附分子和中脑黑质区炎症因子的表达,免疫荧光法检测黑质区胶质细胞活化及多巴胺能神经元存活情况。结果经ATRA预处理的PD小鼠外周调节性T细胞(Tregs)数目增多(2.3±0.21)%;P0.05]。PD1表达上调CD4+:(4.65±0.61)%;CD8+:(3.50±0.31)%;P0.05]。黏附分子(Icam-1:0.37±0.13;Vcam-1:0.32±0.06)及炎症因子(IL-6:0.16±0.05;TNF-α:0.29±0.12)相对表达均下调(P0.05)。黑质区胶质细胞活化减少,多巴胺能神经元存活率提高。小鼠的协调能力转棒停留总时间:(157.5±24.5)s]及自主运动能力运动总距离:(42.58±2.96)m]均得到改善(P0.05)。结论 ATRA可能通过增强Tregs的抑炎效应,间接发挥多巴胺能神经元保护作用。

All-trans retinoic acid exerts a protective effect on dopaminergic neurons by enhancing the anti-inflammatory effect of regulatory T cells

Objective To investigate the effect of all-trans retinoic acid (ATRA) on dopaminergic neurons in mice with Parkinson's disease (PD) and related mechanisms.Methods Wild-type mice were randomly divided into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) control group and ATRA + MPTP group.The behavioral test was performed before and after modeling.Flow cytometry was used to measure peripheral T lymphocyte subsets,real-time quantitative PCR was performed to measure the expression of adhesion molecules in the choroid plexus and inflammatory factors in the substantia nigra,and immunofluorescence assay was used to evaluate the activation of glial cells and the survival of dopaminergic neurons in the substantia nigra.Results The PD mice pretreated with ATRA had a significant increase in the number of peripheral regulatory T cells (2.3％ ±0.21％,P ＜0.05).There was a significant increase in the expression of PD1,with 4.65％ ±0.61％ in CD4 + regulatory T cells and 3.50％ ±0.31％ in CD8 + regulatory T cells (P ＜ 0.05).There were significant reductions in the relative expression of adhesion molecules Icam-1 (0.37 ± 0.13) and Vcam1 (0.32 ±0.06) and inflammatory factors interleukin-6 (0.16 ±0.05) and tumor necrosis factorα (0.29 ±0.12) (P＜0.05).In the substantia nigra,the activation of glial cells was reduced,and the viability of dopaminergic neurons was increased.There were significant improvements in coordinate ability (total time spent on the rotating rod:157.5 ± 24.5 s) and autonomic activity (total movement distance:42.58 ± 2.96 m) in mice.Conclusions ATRA exerts a protective effect on dopaminergic neurons by enhancing the anti-inflammatory effect of regulatory T cells.