康复学报2025，Vol.35Issue(3)：275-283,9.DOI:10.3724/SP.J.1329.2025.03007
侵入性迷走神经电刺激激活小胶质细胞α7nAChR减轻帕金森小鼠纹状体神经炎症的机制研究
Invasive Vagus Nerve Stimulation Activates Microglia α7nAChR to Reduce Striatal Neuroinflammation in Mouse Model of Parkinson's Disease and Its Mechanism
摘要
Abstract
Objective To investigate the mechanism by which invasive vagus nerve stimulation(VNS)activates microglia α7 nicotinic acetylcholine receptor(α7nAChR)to reduce striatal neuroinflammation in mouse model of Parkinson's disease.Methods Forty 8-week-old SPF wild-type male C57BL/6J mice were randomly divided into four groups:Control group,MPTP group,VNS group and Sham group,with 10 mice in each group.The VNS and Sham groups underwent electrode implantation surgery with the same procedures.After a 1-week recovery period post-surgery,the PD model was induced by subcutaneous injection of MPTP saline solution(20 mg/kg)combined with intraperitoneal injection of probenecid(250 mg/kg)in the MPTP,VNS and Sham groups.The equal volume of normal saline was injected in the control group using the same method twice a week for 5 weeks.Concurrently with modeling,the VNS and Sham groups underwent VNS intervention.The VNS group received rectangular wave stimulation,the fre-quency was 30 Hz,the pulse width was 300 us,the current intensity was 2 mA,and the rise and decline time was 5 s.In the Sham group,the current intensity was 0 mA,and the other stimulation parameters were identical to those in the VNS group,once a day.The intervention lasted for 5 weeks.After modeling and intervention,the open field test was used to detect the autonomic motor function of each group.The rotarod test was used to detect the balance and coordination function of each group.The area of tyrosine hydroxylase(TH)positive cells in striatum was detected by immunohistochemistry.The protein expressions of TH and α7nAChR in striatum were detected by Western blot.The expression levels of IL-1β,IL-6 and TNF-α in striatum were detected by ELISA.The number of microglia and α7nAChR positive cells in each group was detected by immunofluorescence staining.Results Compared with the Control group,the autonomous crawling distance decreased more significantly in the MPTP group(P<0.05).Compared with the Sham group,the autonomous crawling distance increased more significantly in the VNS group(P<0.05).Compared with the Control group,the MPTP group had a shorter residence time on the rotarod(P<0.05).Compared with Sham group,the residence time was prolonged in VNS group(P<0.05).Immunohistochemical staining showed that,compared with the Control group,the area of TH-positive cells in the MPTP group decreased more significantly(P<0.05).Compared with the Sham group,the areas of TH-pos-itive cells in the VNS group increased more significantly(P<0.05).Western blot results showed that,compared with the Control group,the MPTP group had more significant reductions in the protein expressions of TH and α7nAChR(P<0.05).Compared with the Sham group,the relative expressions of TH and α7nAChR in the VNS group increased more significantly(P<0.05).ELISA re-sults showed that,compared with the Control group,the MPTP group had more significant increases in the expression levels of pro-inflammatory factors IL-1β,IL-6 and TNF-α(P<0.05).Compared with the Sham group,the expression levels of IL-1β,IL-6 and TNF-α were lower in the VNS group(P<0.05);compared with the Control group,the MPTP group had a more significant increase in the number of IBA-1 positive cells(P<0.05)and a more significant reduction in the number of α7nAChR positive cells(P<0.05).Compared with the Sham group,the VNS group showed fewer IBA-1-positive cells(P<0.05)and more α7nAChR-positive cells(P<0.05).Conclusion VNS can reduce striatal neuroinflammation in mouse model of Parkinson's disease by activating α7nAChR of microglia,thereby preventing the loss of dopaminergic neurons.关键词
帕金森病/神经炎症/迷走神经电刺激/α7nAChR/小胶质细胞Key words
Parkinson's disease/neuroinflammation/vagus nerve stimulation/α7nAChR/microglia引用本文复制引用
耿铫,王瑞宇,朱壮,沈滢,张克忠..侵入性迷走神经电刺激激活小胶质细胞α7nAChR减轻帕金森小鼠纹状体神经炎症的机制研究[J].康复学报,2025,35(3):275-283,9.基金项目
国家自然科学基金面上项目(82071431) （82071431）
