丙戊酸对实验性自身免疫性神经炎大鼠保护作用的机制

目的观察丙戊酸(VAP)对实验性自身免疫性神经炎(EAN)大鼠的保护作用及其机制。方法实验大鼠随机分为VAP高剂量组、VAP低剂量组、EAN模型组、正常组,应用P2 57-81多肽与完全弗氏佐剂的混合液诱导EAN模型。VAP于免疫当天至第15d每天腹腔内注射。观察各组大鼠发病情况和坐骨神经组织病理学变化,检测外周血中Th17细胞和Foxp3+Treg细胞含量,检测淋巴结中TNF-α、IFN-γ、IL-17、TGF-βmRNA表达。结果 VAP高剂量组的最初发病时间迟于EAN组(P<0.05),其高峰期临床评分显著低于EAN组(P<0.05),坐骨神经炎性细胞浸润较EAN组明显减少;VAP高剂量组和低剂量组外周血中Th17细胞比例较EAN组显著减少(P<0.05),Foxp3+Treg细胞比例较EAN组显著增加(P<0.05),淋巴结中促炎细胞因子TNF-α、IFN-γ及IL-17mRNA表达与EAN组比较明显下降(P<0.05),VAP高剂量组抑炎细胞因子TGF-βmRNA表达与EAN组比较明显升高(P<0.05)。结论 VAP对EAN有治疗作用,这种作用可能与其能够增加Foxp3+Treg细胞和抑炎细胞因子TGF-β含量、减少TH17细胞含量和促炎细胞因子的表达有关。

Effects of valproic acid on experimental autoimmune neuritis in Lewis rats

Objective To explore the effects and mechanism of valproic acid （VAP） on experimental autoimmune neuritis （EAN）. Methods Lewis rats were randomly divided into VAP high-dose group, VAP low-dose group, EAN model group and normal group. EAN model was established by immunizing Lewis rats with peripheral nerve myelin sheath antigen （ P257 -81 ） peptide and completed Freund＇ s adjuvant （ CFA ）. VAP high-dose group and low-dose group were intraperitoneally injected every day with 300mg . kg . d-1 or 150 mg. kg. d -1 VAP, and the EAN model group and normal group were intraperitoneally injected with the same volume of DHEA once daily from 0 day to 15 day post-immunization. The effects were assessed in terms of appearance of clinical signs, histopathology in sciatic nerve sections, Th17 cells and Foxp3＋ Treg cells in peripheral blood, mRNA levels of inflammatory cytokines ： TNF-α, IFN-γ, IL-17 and TGF-β in the lymph nodes. Results The time when VAP high-dose group first neuro- logical sign was seen was later than EAN group. The maximal neurological score and inflammatory cell infiltrate in sciatic nerve of high-dose group were lower than EAN group. In peripheral blood, Foxp3 ＋ Treg cells of high-dose group and low-dose group were increased but Th17 cells were decreased. Furthermore, TNF-α, IFN-γ, IL-17mRNA levels in the lymph nodes of high-dose group and low-dose group were significantly suppressed. But TGF-β mRNA lev- els of high-dose group were increased. Conclusion VAP can increase Foxp3＋ Treg cells and TGF-β mRNA levels, but decrease Thl7 cells and pro-inflammatory cytokines mRNA levels, so VAP can treat EAN effectively.