血管活性肠肽(VIP)对实验性自身免疫性脑脊髓炎(EAE)大鼠脑组织IL-17A含量的影响

Effect of vasoactive intestinal peptide(VIP) on the content of IL-17A in the brain tissue of rats with experimental autoimmune encephalomyelitis(EAE)

目的探讨血管活性肠肽(vasoactive intestinal peptide,VIP)对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠脑组织IL-17A含量的影响。方法 60只健康雌性Wistar大鼠随机分成正常对照组、EAE对照组、VIP低剂量防治组和VIP高剂量防治组。利用髓鞘碱性蛋白(MBP)+完全福氏佐剂(CFA)诱导建立EAE模型。自造模当日起,每隔一日分别对VIP低、高剂量防治组大鼠腹腔注射VIP 4nmol/kg(0.2 m L)、16 nmo L/kg(0.8 m L),正常对照组及EAE对照组注射0.8 m L生理盐水,连续10 d。观察大鼠发病情况;ELISA法检测脑组织匀浆中IL-17A因子含量变化;免疫组化技术,利用抗胶质纤维酸性蛋白抗体(GFAP)检测脑组织内的星型胶质细胞活化情况。结果 VIP各剂量防治组大鼠发病潜伏期延长、进展期缩短、发病高峰期神经功能障碍评分(NDS)降低,脑组织匀浆中IL-17A含量降低,活化的星型胶质细胞即GFAP^+细胞量减少,且各剂量组间存在一定剂量依赖关系。结论 VIP通过降低脑组织中IL-17A含量、抑制星型胶质细胞活化,发挥对EAE的防治作用。

Objective To explore the effect of vasoactive intestinal peptide（ VIP） on the content of IL-17 A in the brain tissue of rat models of experimental autoimmune encephalomyelitis（ EAE）. Methods Sixty healthy female Wistar rats were randomly divided into normal control group,EAE control group,low-dose VIP group and high-dose VIP group.Ten healthy guinea pigs were used to prepare anti- IL-17 A antibody. Myelin basic protein（ MBP） ＋ complete adjuvant（ CFA） were used to establish the EAE model. Since the first day of modelling,the low-dose and high-dose VIP groups received intraperitoneal injection of VIP 4 nmol / kg（ 0. 2 m L） and 16 nmol / kg（ 0. 8 m L）,respectively,every other day for 10 consecutive days. The normal control group and EAE group were injected with 0. 8 m L saline instead of VIP. The incubation period,progression and the peak of neurological dysfunction scores（ NDS） of the rats were recorded. The levels of IL-17 A in the brain tissue was determined by ELISA assay,and the GFAP-＋astrocyte activation in brain at morbidity peak in the rats was examined using anti-GFAP（ glial fibrillary acidic protein） antibodies. Results The incubation period were extended,the progression period was shortened and the peak neuological dysfunction score（ NDS） was decreased in the VIP-treated groups,in a dose-response relationship. The cytokine levels of IL-17 A and the astrocyte activation degree in brain tissue were reduced in each VIP dose group,in a dose-response relationship. Conclusions VIP exerts therapeutic effect on experimental autoimmune encephalomyelitis through lowering the IL-17 A content and inhibition of astrocyte activation in the brain tissue.