中国药理学通报2018,Vol.34Issue(2):191-197,7.DOI:10.3969/j.issn.1001-1978.2018.02.010
辣椒素通过抑制自噬活性抑制实验性自身免疫性神经炎
Capsaicin inhibits experimental autoimmune neuritis in rats through inhibition of autophagy activity
摘要
Abstract
Aim To observe the effect of capsaicin on the experimental autoimmune neuritis (EAN) in rats and explore the mechanism.Methods To induce EAN,male Lewis rats were immunized with peripheralnerve myelin sheath antigen (P257481) peptide and complete Freund's adjuvant (CFA) mixed liquor.Rapamycin (RAPA,2.5 mg · kg-1) was administered by intraperitoneal injection 0.5 h after immunization and capsaicin (1 mg · kg-1 · d-1) was administered by intragastric administration 1.0 h after immunization for 15 days.The incidence and clinical characteristics of EAN were observed.The clinical scores of neurological signs were completed and body weight was measured.Pathological morphology of sciatic nerve was observed by HE staining and Lauck fast blue staining.Ultrastructure of sciatic nerve was observed by transmission electron microscope.Levels of serum tumor necrosis factor alpha (TNF-α),interferon gamma (IFN-γ),interleukin 1β (IL-1β) and intedeukin-6 (IL-6) were tested by enzyme linked immunosorbent assay (ELISA).Expressions of autophagy related protein were measured by Western blot.Results Compared with EAN group,the clinical scores of neurological signs significantly decreased from day 7 to day 16 of post-immunization (P < 0.05),body weight significantly increased from day 3 to day 16 of post-immunization (P < 0.05),demyelination obviously decreased,inflammatory cell infiltration number obviously decreased (P < 0.05),the levels of TNF-α,IFN-γ,IL-1β and IL-6 significantly decreased (P < 0.05),the number of autophagosome in axon of sciatic nerve significantly decreased (P < 0.05),and expressions of Beclin-1 and LC3-Ⅱ and the ratio of LC3-Ⅱ and LC3-Ⅰ were significantly down-regulated,and the expression of p62 was significantly up-regulated (P < 0.05) in EAN + capsaicin group.Rapamycin partially reversed the action of capsaicin.Conclusions Capsaicin inhibits EAN in rats,and the mechanism may be related with the inhibition of autophagy activity.关键词
辣椒素/实验性自身免疫性神经炎/肿瘤坏死因子-α/干扰素-γ/白介素/自噬/自噬相关蛋白Key words
capsaicin/experimental autoimmune neuritis/tumor necrosis factor alpha/interferon gamma/interleukin/autophagy/autophagy related protein分类
医药卫生引用本文复制引用
周寿红,薛瑞瑞,郭潇潇,盛思敏,杜倩,夏嘉辉,肖婷,林芬..辣椒素通过抑制自噬活性抑制实验性自身免疫性神经炎[J].中国药理学通报,2018,34(2):191-197,7.基金项目
湖南省自然科学基金资助项目(No 2016JJ2110) (No 2016JJ2110)
湖南省教育厅优秀青年基金资助项目(No 15B208) (No 15B208)
湖南省2017年研究生科研创新项目(No CX2017B547) (No CX2017B547)
南华大学大学生研究性学习和创新性实验计划项目(No 2016NH056XJXZ) (No 2016NH056XJXZ)