中国药理学通报2025，Vol.41Issue(5)：851-860,10.DOI:10.12360/CPB202409081
藁本内酯通过AIM2/caspase-1信号通路抑制炎症反应改善远端大脑中动脉闭塞小鼠髓鞘脱失
Ligustilide improves demyelination of dMCAO mouse model by inhibiting inflammation through AIM2/caspase-1 signaling pathway
摘要
Abstract
Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P＜0.05),the expression of IBA1 in CX decreased(P＜0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P＜0.01).The results of ELISA showed that the levels ofTNF-α(P＜0.01),IL-6(P＜0.01),IL-1β(P＜0.05)and IL-17A(P＜0.01)significantly decreased,while the ex-pression of BDNF increased(P＜0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P＜0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.关键词
藁本内酯/脱髓鞘/炎性反应/dMCAO/小胶质细胞/AIM2/caspase-1信号通路Key words
ligustilide/demyelination/inflammatory re-sponse/dMCAO/microglia/AIM2/caspase-1 signaling pathway引用本文复制引用
梁亚杰,王青,刘健,陈莹,张紫薇,蒲萌,汤亿彬,张海飞,宋国斌,马存根..藁本内酯通过AIM2/caspase-1信号通路抑制炎症反应改善远端大脑中动脉闭塞小鼠髓鞘脱失[J].中国药理学通报,2025,41(5):851-860,10.基金项目
国家自然科学基金资助项目(No 81903596) （No 81903596）
山西省中医药管理局中医药创新团队(No zyytd2024039) （No zyytd2024039）
山西省回国留学人员科研资助项目(No 2022-165) （No 2022-165）
山西省卫健委医学科技领军团队项目(No 2020TD05) （No 2020TD05）
国家中医药管理局科研课题(No 2023ZYYDA2038,2023ZYYB040) （No 2023ZYYDA2038,2023ZYYB040）
