丙戊酸对实验性自身免疫性神经炎大鼠保护作用的机制  

Effects of valproic acid on experimental autoimmune neuritis in Lewis rats

作　　者：贲莹[1] 高长玉[2] 张凤华[1] 梁文杰[1] 贺明[1] 

机构地区：[1]河北医科大学中西医结合学院,石家庄050091 [2]河北医科大学第二医院神经内科

出　　处：《脑与神经疾病杂志》2013年第2期141-144,共4页Journal of Brain and Nervous Diseases

基　　金：河北省卫生厅科研基金项目(20110036)

摘　　要：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。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.

关 键 词：丙戊酸 实验性自身免疫性神经炎 TH17细胞 Foxp3+ TREG细胞 细胞因子 

分 类 号：R744.5[医药卫生—神经病学与精神病学]