大麻素1型受体过表达对实验性自身免疫性脑脊髓炎小鼠的免疫调节

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)小鼠细胞免疫调节的影响。方法 选用C57B/L6小鼠制备EAE小鼠模型,采用质粒转染技术制备CB1R过表达组。观察假手术组和CB1R过表达组小鼠的神经功能缺损症状和体质量变化；用ELISA法检测EAE小鼠脊髓、脾脏中细胞因子 INF-γ、IL-6、IL-10、IL-17、IL-1β、TNF-α浓度的变化。结果 与相同时间点的假手术组相比,CB1R过表达组出现神经功能缺损的时间及症状严重程度和体质量减轻程度显著降低(P＜0.05)。假手术组和CB1R过表达组中,细胞因子在中枢神经系统和外周免疫组织的分布不相同。与假手术组相比,CB1R过表达组EAE小鼠脊髓组织中IL-10的浓度显著升高(P＜0.01),而INF-γ、IL-6、IL-17、IL-1β、TNF-α的浓度显著降低(P＜0.05)。结论 CB1R过表达对EAE小鼠中枢神经系统炎性损伤的保护作用,可能通过上调抑炎因子,下调促炎因子的表达实现。
Objective To investigate the effect of cannabinoid 1 receptor(CB1R) over-expression on immunomodulation in mice with experimental autoimmune encephalomyelitis(EAE). MethodsEAE was induced in C57B/L6 mice, CB1R over-expression was prepared by plasmid transfection. The change of neurological deficit and the body weight were compared between sham group and over-expression group. Serum cytokines INF-γ, IL-6, IL-10, IL-17, IL-1β and TNF-α were measured by ELISA. Results The onset time of neurologic impairment, the severity of symptoms and weight loss were significantly lower in CB1R over-expression group than sham group(P＜0.05). The cytokine profile was different between central nervous system and peripheral immune tissue in both groups. Compared with sham group, the level of IL-10 in spinal cord was significantly higher(P＜0.01) and INF-γ, IL-6, IL-17, IL-1β and TNF-α were significantly lower(P＜0.05). ConclusionCB1R can protect central nervous system from inflammatory injury in EAE mice by up-regulation of inhibiting inflammatory cytokines and down-regulation of proinflammatory cytokines