白藜芦醇通过SIRT1/AMPK信号通路减轻MPTP诱导的小鼠多巴胺能神经元丢失

目的观察白藜芦醇(RV)对帕金森病(PD)小鼠的神经保护作用,并探索其发挥神经保护作用的可能机制。方法将48只小鼠随机分为CON组、MPTP组、RV+MPTP组和EX527+RV+MPTP组,每组12只。腹腔注射MPTP建立PD小鼠模型,并给予RV灌胃、SIRT1特异性抑制剂EX257腹腔注射处理,利用免疫荧光、western blot等检测相关蛋白表达。结果给予RV后,与MPTP组相比,RV+MPTP组SIRT1蛋白表达显著增加(P0.001),p-AMPK蛋白水平显著升高(P0.01),Cleaved caspase 3蛋白水平显著下降(P0.01),小鼠黑质区TH阳性神经元丢失率明显降低,纹状体组织中TH蛋白表达显著增加(P0.01)。给予EX527后,阻断了RV的上述作用,p-AMPK蛋白水平显著降低(P0.01),Cleaved caspase 3显著升高(P0.01),小鼠黑质区TH阳性神经元丢失率明显升高,纹状体组织中TH蛋白表达显著下降(P0.001)。结论 RV可能通过激活SIRT1/AMPK信号通路,SIRT1与AMPK相互调控,减少MPTP小鼠黑质区多巴胺能神经元丢失。

Neuroprotective effect of resveratrol against MPTP-induced dopaminergic neuronal loss via the SIRT1/AMPK signaling pathway in mice

Objective To investigate the neuroprotective effect of resveratrol (RV) in mice with Parkinson''s disease (PD) and its possible mechanisms.Methods A total of 48 mice were divided into CON group, MPTP group, RV+MPTP group, and EX527+RV+MPTP group, with 12 mice in each group. Intraperitoneal injection of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the mouse model of PD, and RV gavage and intraperitoneal injection of the silent information regulation 2 homolog 1 (SIRT1) specific inhibitor EX527 were given. Immunofluorescence assay and Western blot were performed to measure the expression of related proteins.Results After administration of RV, compared with the MPTP group, the RV+MPTP group showed significantly increased protein expression of SIRT1 and p-AMP-activated protein kinase (AMPK), significantly reduced protein expression of cleaved caspase 3, significantly reduced TH-positive neuronal loss in the substantia nigra, and significantly increased expression of TH protein (all P<0.01). The administration of EX527 inhibited the above effects of RV and caused a significant reduction in the protein expression of p-AMPK (P<0.01), as well as significantly increased protein expression of cleaved caspase 3 (P<0.01), significantly increased TH-positive neuronal loss in the substantia nigra, and significantly reduced expression of TH protein (P<0.001).Conclusions RV can activate the SIRT1/AMPK signaling pathway, regulate SIRT1 and AMPK, and thus reduce dopaminergic neuronal loss in the substantia nigra of mice treated with MPTP.