丙戊酸抑制大鼠实验性自身免疫性神经炎机制研究

Inhibition Mechanism of Valproic Acid on Experimental Autoimmune Neuritis in Rats

目的探讨丙戊酸(VPA)抑制大鼠实验性自身免疫性神经炎(experimental autoimmune neuritis,EAN)的机制。方法 36只实验大鼠随机分为治疗组、模型组和正常组,每组12只,应用P257-81多肽与完全弗氏佐剂的混合液免疫治疗组和模型组大鼠。治疗组于免疫当天至第15天每天腹腔内注射300 mg/kg丙戊酸钠,模型组、正常组同时点注射等量的PBS。观察发病情况,坐骨神经病理及免疫组化改变,检测外周血中Th17和Foxp3+Treg细胞含量及淋巴结中肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)、白介素17(IL-17)和β型转化生长因子(TGF-β)mRNA表达水平。结果治疗组的最初发病时间迟于模型组,其高峰期神经系统体征评分显著低于模型组,坐骨神经炎性细胞浸润较模型组明显减少(P<0.05)。模型组与治疗组外周血中Th17、Foxp3+Treg细胞所占百分比均高于正常组,治疗组外周血中Th17细胞所占百分比低于模型组,Foxp3+Treg细胞所占百分比高于模型组(P<0.05)。治疗组淋巴结中TNF-α、IFN-γ和IL-17的mRNA表达水平低于模型组,TGF-β的mRNA表达水平高于模型组(P<0.05)。结论丙戊酸能够抑制EAN大鼠的自身免疫反应,对EAN有治疗作用。

Objective To explore the inhibition mechanism of Valproic acid （VPA） on experimental autoimmune neuritis （EAN） in rats. Methods Thirty-six experimental rats were randomly divided into treatment group （n = 12） , the model group （n = 12） and normal group （n = 12）. Treatment group and model group were immunized with peripheral nerve myelin sheath antigen （P2 57-81） peptide and complete Freundg adjuvant （CFA） mixed liquor. Treatment group was intraperitoneally injected every day with 300 mg/kg of Sodium Valproate, and the model group and normal group were intraperitoneally injected with the same volume of PBS once daily at the same time from day 0 to day 15 of post-immunization. The incidence, sciatic nerve pathology and immunohistochemisty changes were observed, and content of Thl7 ceils and Foxp^3＋ Treg cells in peripheral blood, mRNA expression levels of inflammatory cytokines： TNF-α, IFN-γ, interleukin-17 and TGF-β in the lymph nodes were detected. Results The first disease time of treatment group was later than that of model group, the maximal neurological score of treatment group was significantly lower than that of model group, and inflammatory cell infiltrate in sciatic nerve of treatment group were also significantly reduced than that of model group （P 〈 0.05）. Thl7 cells and Foxp^3＋ Treg cells in peripheral blood of model group and treatment group were higher than those of normal group, percentage of Thl7 cells in peripheral blood of treatment group was lower than that of model group, and Foxp3 ~ Treg ceils in peripheral blood of treatment group was significantiy higher than that of model group（P 〈 0.05 ）. The mRNA levels of TNF-α, IFN-γ, IL-17 in the lymph nodes of treatment group were significantly higher than those of model group, while TGF-β mRNA level of treatment group was significantly lower than that of model group（P 〈0.05）. Conclusion Valproic acid can effectively suppress autoimmune response in EAN which can treat EAN effectively.