摘要
目的从Ⅰ型辅助T细胞(Th1)、17型辅助T细胞(Th17)细胞除极角度探讨丙戊酸(VPA)干预实验性自身免疫性神经炎(EAN)的机制。方法实验大鼠随机分为VPA治疗组、EAN组、正常组,应用周围神经髓鞘抗原(P257-81)多肽与完全弗氏佐剂的混合液免疫VPA治疗组和EAN组大鼠。VPA治疗组大鼠于免疫当天至第15天每天腹腔内注射300mg·kg-1丙戊酸钠。观察发病情况,坐骨神经电生理改变及组织病理学变化,检测腹股沟淋巴结中IFN-γ、IL-17 mRNA水平。结果 VPA治疗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),坐骨神经复合肌肉动作电位(CMAP)的波幅较EAN组明显升高,潜伏期和时限显著缩短(P<0.05)。髓鞘脱失和炎性细胞浸润较EAN组明显减少(P<0.05)。淋巴结中IFN-γ、IL-17mRNA表达明显下降(P<0.05)。结论 VPA通过影响Th1、Th17细胞除极,使IFN-γ、IL-17分泌下降,从而抑制EAN大鼠的自身免疫反应。
Objective To explore the effects and mechanism of valproic acid (VPA) on the Th1/Th17 cells polarization in EAN. Methods Lewis rats were randomly divided into VPA treatment group, the EAN group and normal group. EAN model was established by immunizing Lewis rats with peripheral nerve myelin sheath antigen ( P2 57-81 ) peptide and complete Freund' s adjuvant ( CFA ). VPA treatment group was intraperitoneally injected every day with 300mg . kg-1 VPA, and the EAN group and normal group were intraperitoneally injected with the same volume of PBS once daily from day 0 to day 15 post-immunization. The effects were assessed in terms of appearance of clinical signs, electrophysiology and histopathotogy of the sciatic nerves, mRNA levels of inflammatory cytokines: IFN-y, IL-17 in the lymph nodes. Results The time when VPA treatment group first neurological sign was seen was later than EAN group. The maximal neurological score and inflammatory cell infiltrate in sciatic nerve of VPA treatment group were lower than EAN group. Amplitude of compound muscle action potential (CMAP) of the sciatic nerves from VPA treatment group was increased, prolongation of latency and duration of the sciatic nerves reduced. IFN-y , IL-17mRNA levels in the lymph nodes of VPA treatment group significantly suppressed. Conclusions VPA could effectively suppress autoimmune response in EAN. The protective effect of VPA could be associated with the inhibition of IL-17, IFN-y, through the polarization of Th1/Th17 cells.
出处
《脑与神经疾病杂志》
2014年第1期33-36,共4页
Journal of Brain and Nervous Diseases
基金
河北省卫生厅科研基金项目(20110036)