Rα97-116(V108A)鼻黏膜耐受对实验性自身免疫性重症肌无力T-bet及GATA-3的影响  

Effect of nasal tolerance with Rα97-116(V108A) on the expression of transcription factor T-bet/GATA-3 in experimental autoimmune myasthenia gravis

作　　者：谢娟[1] 罗六一 许文华[1] 赵江明[1] 杨毅[1] 任明山[1] 

机构地区：[1]安徽医科大学附属省立医院神经内科,合肥230001

出　　处：《安徽医科大学学报》2009年第1期45-48,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金资助项目(编号:070413260X);安徽省人才开发基金资助项目(编号:2005Z041);安徽省卫生厅科研基金资助项目(编号:06B0033)

摘　　要：目的探讨Rα97-116(V108A)鼻黏膜耐受对实验性自身免疫性重症肌无力(EAMG)鼠模型的治疗作用及对转录因子T-box家族成员之一(T-bet)和可与DNA序列[A/T(GATA)A/G]结合的Ⅳ型锌指蛋白之一(GATA-3)的影响机制。方法将成模Lewis大鼠随机分为:EAMG模型组(A组)和鼻黏膜耐受组(B组),并设正常对照组(C组)。B组给予Rα97-116(V108A)30μg共10d,记录A、B两组大鼠临床评分。采用逆转录-聚合酶链反应(RT-PCR)检测三组动物外周血单个核细胞(PBMCs)中T-bet及GATA-3 mRNA表达,酶联免疫吸附法(ELISA)测定血浆中白介素-4(IL-4)、干扰素-γ(IFN-γ)表达水平及乙酰胆碱受体抗体IgG(AchR-AbIgG)含量。结果B组临床评分及AchR-AbIgG含量较A组显著降低(P<0.05);A组T-bet和GATA-3 mRNA、IL-4、IFN-γ表达水平明显高于C组,与A组相比,B组的表达水平明显降低(P<0.05),B组、C组之间表达水平无统计学差异(P>0.05);EAMG大鼠IL-4水平和IFN-γ水平分别与GATA-3和T-bet mRNA表达呈正相关(r=0.90,P<0.05;r=0.753,P<0.05)。结论Rα97-116(V108A)鼻黏膜耐受减轻EAMG的肌无力症状,其作用机制可能与其下调T-bet和GATA-3的表达,抑制异常Th1和Th2反应从而下调AChR特异性T和B细胞异常的免疫应答反应有关。Objective To investigate the mechanism of nasal tolerance with synthetic peptide Rα97-116（V108A） in treatment of experiment autoimmune myasthenia gravis （EAMG）. Methods Model Lewis rats were divided into EAMG group （group A） and nasal tolerance treatment group （group B）, control group （group C）was also set up. Rα97-116（V108A） 30 μg was dropped in the nasal cavities of Lewis rats in group B for 10 consecutive day. Since nasal administration, clinical score was evaluated every other day. The expression levels of transcription factor T- bet/GATA-3 in PBMCs were measured by RT-PCR. IL-4, IFN-γ, AchR-Ab IgG in plasma were detected by ELISA. Results The clinical score and the amount of anti-AchR IgG between group A and B were different signifi- cantly （P 〈 0. 05 ）. The expression levels of T-bet/GATA-3 mRNA, IL-4 and IFN-γ in group A were much higher than those in group C （ P 〈 0. 05 ） ; while T-bet/GATA-3 mRNA, IL-4 and IFN-γ expression were obviously decreased after nasal tolerance with Rα97-116 （ V108A ） （ P 〈 0. 05 ）, there were not significant difference between group B and C （P 〉 0. 05 ）. In EAMG, the expression intensity of IL-4 was positively correlated with that of GATA- 3 mRNA （r = 0. 90,P 〈0. 05 ）, the same as IFN-γ and T-bet mRNA （ r = 0. 753, P 〈 0. 05 ）. Conclusions Nasal tolerance with Rα97-116（VlO8A） could surpress ongoing EAMG, which may be related to the decrease of T-bet/ GATA-3 expression and downregulation of AChR-specific B-cell responses and AChR-reactive T-cell function.

关 键 词：重症肌无力 免疫耐受 疾病模型 动物 转录因子 

分 类 号：R746.1[医药卫生—神经病学与精神病学] R392.11[医药卫生—临床医学]