大麻素1型受体过表达在实验性自身免疫性脑脊髓炎小鼠中的作用

目的 探讨大麻素1型受体(cannabinoid 1 receptor,CB1R)过表达对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)小鼠神经功能的影响及其作用机制.方法 选取24只C57B/L6小鼠,采用MOG3s-55免疫诱导构建EAE小鼠模型,随机分为2组,一组采用质粒转染技术使小鼠脊髓组织CB1R过表达,另一组给予溶剂作为对照.观察对照组和CB1R过表达组EAE小鼠的神经功能缺损症状,采用蛋白质印迹法检测小鼠脊髓组织中CB1R蛋白的表达,采用酶联免疫吸附试验检测小鼠脊髓组织中细胞因子白介素(IL)-10、IL-17、ID6、肿瘤坏死因子α (TNF-α)的浓度.结果 免疫后第14、28天时CB1R过表达组EAE小鼠发生神经功能缺损的程度低于对照组(P＜0.05).与对照组相比,CB1R过表达组EAE小鼠脊髓组织中CB1R蛋白的表达水平升高(P＜0.01),IL-10的浓度升高(P＜0.05),而IL-17、ID6、TNF-α的浓度降低(P＜0.05,P＜0.01).结论 中枢神经细胞中CB1R的过表达能够延缓EAE的发生和发展,这种作用可能是通过免疫调节实现的.

Effect of cannabinoid 1 receptor overexpression on mice with experimental autoimmune encephalomyelitis

Objective To explore the effect of cannabinoid 1 receptor (CB1R) overexpression on the neurological function of mice with experimental autoimmune encephalomyelitis (EAE) and the related mechanism.Methods Twenty-four C57B/L6 mice were selected to prepare EAE models by MOG35-55 immunization and were divided into two groups.CB1R was overexpressed in mouse spinal cord tissue by plasmid transfection technique in CB1R overexpression group,and the other group was given solvent as control.The neurological deficits of mice were observed in control group and CB1R overexpression group.The expression of CB1R in the spinal cord of mice were detected by Western blotting analysis.The concentrations of interleukin (IL)-10,IL-17,IL-6,and tumor necrosis factor-α (TNF-α) were measured by ELISA.Results The degree of neurological deficit of mice in the CB1 R overexpression group was significantly lower than that in the control group on 14th and 28th day after immunization (P＜0.05).Compared with the control group,the expression of CB1 R protein in spinal cord in the CB1R overexpressing group was significantly increased (P＜ 0.01),the concentration of IL-10 was significantly increased (P＜0.05),and the concentrations of IL-17,IL-6,and TNF-α were significantly decreased (P＜ 0.05,P＜ 0.01).Conclusion CB1R overexpression in central nervous cells can postpone the development and progression of EAE in mice,which may be achieved through immuomodulation.