白藜芦醇改善α-突触核蛋白A53T转基因小鼠运动功能障碍和调节外周免疫的作用研究

Effect of resveratrol on motor dysfunction and peripheral immunity in α-synuclein A53T mice

目的研究白藜芦醇(resveratrol,RES)对α-突触核蛋白(α-synuclein,α-Syn)A53T转基因小鼠运动功能障碍及外周免疫的影响。方法选取8月龄的A53T转基因小鼠,随机分成4组:对照组(WT)、对照治疗组(WT+RES)、模型组(PD)、模型治疗组(PD+RES)。治疗组每3 d灌胃RES,用药3个月;对照组和模型组给予等量生理盐水。通过爬杆实验、转棒实验、前脚抓力实验、四肢抱紧实验检测各组小鼠运动水平。流式细胞仪检测小鼠T淋巴细胞亚群,酶联免疫吸附试验(ELISA)检测小鼠血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-18(IL-18)以及转化生长因子-β(TGF-β)的水平。结果与对照组相比,模型组运动功能评分均较低;与模型组相比,模型治疗组运动功能评价显著改善。流式结果显示,与对照组比,模型组小鼠外周T细胞占比、CD4^(+)T细胞占比、CD4^(+)/CD8^(+)比值均降低,CD8^(+)T细胞占比无统计学意义。与模型组相比,模型治疗组T淋巴细胞占比和CD4^(+)T细胞占比均显著升高,有统计学意义,CD4^(+)/CD8^(+)比值也升高,但差异无统计学意义。外周血血清ELISA结果显示,与对照组相比,模型组小鼠IL-6、IL-18均升高,TGF-β降低,TNF-α浓度无统计学差异。与模型组相比,模型治疗组IL-6、IL-18浓度显著下降,TGF-β有所上升,结果无统计学意义。结论RES通过调节小鼠外周免疫,减少神经炎症反应,从而显著改善A53T转基因小鼠的运动功能障碍。

Objective To illustrates the effect of resveratrol on motor dysfunction and peripheral immunity inα-synuclein A53T mice.Methods Eight-month-old A53Tα-syn transgenic mice were randomly divided into four groups:model group(PD),model treatment group(PD+RES),control group(WT)and control treatment group(WT+RES).The treatment groups were given Resveratrol(RES)by gavage every 3 days for 11 months,while the control and model groups were given an equal volume of normal saline.The motoric function of the animals was analyzed with a forelimb grip strength test,Rotarod test,and Pole climbing test.The proportion of T lymphocyte subsets in different groups of mice was detected by flow cytometry.IL-6,TNF-α,IL-18 and TGF-βin each group were detected by an ELISA kit.Results the motor function scores in the PD group were worse than those in the WT group.Compared with the PD group,the motor function score of the PD+RES group was significantly improved.The flow cytometry result showed that compared with the WT group,the T lymphocyte ratio,CD4^(+)T cell ratio,and CD4^(+)/CD8^(+)ratio were less in the PD group,while the CD8^(+)T cell ratio was not significantly different.After RES treatment,T lymphocytes,CD4^(+)cells,and the CD4^(+)/CD8^(+)ratio were significantly greater in the PD+RES group than the PD group.The ELISA result showed that compared with the WT group,the IL-6 and IL-18 levels in the PD group were greater,the TGF-βlevel were less,and the TNF-αlevel showed no significant statistical difference.After RES treatment,compared with the PD group,the IL-6 and IL-18 levels in the PD+RES group were significantly less,while the TGF-βlevel was greater;however,the result showed no statistical difference.Conclusions Resveratrol can reduce motor disorders,regulate peripheral immune function,and effectively reduce neuroinflammation.