TRPV1蛋白对自身免疫性脑脊髓炎进展及Th1和Th17细胞分化的影响  

Effect of TRPV1 protein on the progression of autoimmune encephalomyelitis and the differentiation of Th1 and Th17 cells

作　　者：王布飞 陈聪 李建红 WANG Bufei;CHEN Cong;LI Jianhong(Department of Neurology,The Second Affiliated Hospital of Hainan Medical University,Haikou 570300,China)

机构地区：[1]海南医科大学第二附属医院神经内科,海口570300

出　　处：《中国医科大学学报》2025年第4期323-327,332,共6页Journal of China Medical University

基　　金：海南省卫生健康行业科研项目(21A200002)。

摘　　要：目的探讨瞬时感受器电位香草酸受体1(TRPV1)蛋白对实验性自身免疫性脑脊髓炎(EAE)进展的影响及其机制。方法将36只C57BL/6野生型小鼠随机分为对照组、模型组、模型+TRPV1抑制剂组,每组12只。EAE模型构建采用皮下注射髓磷脂少突胶质细胞糖蛋白35-55混合结核杆菌乳剂,联合腹腔注射百日咳毒素。模型+TRPV1抑制剂组小鼠每日连续腹腔注射TRPV1抑制剂辣椒平溶液(30 mg/kg)。连续35 d观察并评估小鼠EAE症状。第35天处死小鼠,取脊髓组织,采用劳克坚牢蓝染色评估脊髓髓鞘脱失,采用流式细胞术分析脊髓单核细胞中CD4^(+)T细胞分化情况,采用Western blotting检测TRPV1蛋白和炎症反应信号蛋白表达。结果与对照组相比,模型组小鼠神经功能评分增加,脊髓组织出现明显的髓鞘脱失。流式细胞术结果显示,模型组小鼠CD4^(+)T细胞向Th1和Th17细胞分化比例增加。与模型组相比,模型+TRPV1抑制剂组小鼠神经功能评分降低,脊髓中炎性细胞因子浸润与髓鞘脱失明显减少,CD4^(+)T细胞向Th1和Th17细胞分化比例减少。TRPV1抑制剂明显抑制了TRPV1蛋白表达并降低了p-NF-κB、caspase-1和NLRP3蛋白表达。结论TRPV1蛋白对EAE进展起重要作用,抑制TRPV1蛋白表达能够抑制Th1和Th17细胞分化,减少脊髓组织髓鞘脱失。Objective To explore the effect of transient receptor potential vanilloid 1(TRPV1)protein on experimental autoimmune encephalomyelitis(EAE)progression and its underlying mechanism.Methods Thirty-six C57BL/6 mice were randomly divided into the control,model,and model+TRPV1 inhibitor groups,with 12 mice in each group.The EAE model was established through subcutaneous injection of myelin oligodendrocyte glycoprotein(MOG)35-55 mixed with a tuberculosis bacillus emulsion,combined with an intraperitoneal injection of pertussis toxin.Mice in the model+TRPV1 inhibitor group were administered a daily intraperitoneal injection of TRPV1 inhibitor capsazepine solution at a dose of 30 mg/kg for 35 d.EAE symptoms were observed and assessed.On day 35,the mice were sacrificed,and spinal cord tissues were collected.Luxol fast blue staining was used to evaluate demyelination in the spinal cord,and flow cytometry was performed to analyze CD4^(+)T cell differentiation in the spinal cord.Western blotting was performed to detect TRPV1 and inflammatory response signaling protein expressions.Results Compared with the control group,mice in the model group showed increased neurological function scores and significant demyelination in the spinal cord.The flow cytometry results showed an increased proportion of CD4^(+)T cells differentiating into Th1 and Th17 cells in the model group.Compared with the model group,mice in the model+TRPV1 inhibitor group exhibited decreased neurological function scores,reduced inflammatory cytokine infiltration and demyelination in the spinal cord,and a decreased proportion of CD4^(+)T cells differentiating into Th1 and Th17 cells.TRPV1 protein expression in the model+TRPV1 inhibitor group was significantly inhibited,whereas p-NF-κB,caspase-1,and NLRP3 protein expressions were reduced.Conclusion TRPV1 plays a significant role in EAE progression.TRPV1 inhibition can inhibit the differentiation of Th1 and Th17 cells and reduce demyelination in spinal cord tissues.

关 键 词：瞬时感受器电位香草酸受体1 自身免疫性脑脊髓炎 CD4+T细胞 炎症 

分 类 号：R744[医药卫生—神经病学与精神病学]