鼻黏膜耐受对实验性重症肌无力大鼠胸腺细胞凋亡的影响  

Effects of nasal immune tolerance on thymocyte apoptosis in experimental autoimmune myasthenia gravis rats

作　　者：张立新[1] 任明山[1] 熊小平[1] 贾雪梅[2] 桂丽[2] 黄大可[2] 

机构地区：[1]安徽医科大学附属省立医院神经内科,合肥230001 [2]安徽医科大学基础医学院综合实验室,合肥230032

出　　处：《免疫学杂志》2010年第3期206-210,共5页Immunological Journal

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

摘　　要：目的探讨鼻黏膜耐受处理对实验性自身免疫性重症肌无力(EAMG)大鼠胸腺细胞凋亡及Caspase-3表达的影响。方法将实验大鼠随机分为正常对照组、EAMG组和耐受组,将EAMG组及耐受组大鼠采用Rα97-116肽段多点皮下注射法制备成EAMG大鼠模型后,再将耐受组大鼠经鼻腔滴注Rα97-116(V108A)行免疫耐受处理,10d后评估疗效(临床症状、体质量、抗体滴度等),并采用TUNEL法计数对照组、EAMG组及耐受组大鼠胸腺细胞的凋亡程度,用免疫组化法检测3组大鼠胸腺淋巴细胞内Caspase-3的表达,并分析其阳性细胞染色强度。结果 EAMG组大鼠胸腺细胞的凋亡数较对照组显著减少,鼻黏膜耐受处理能明显促进EAMG大鼠胸腺细胞的凋亡,并改善EAMG大鼠的肌无力症状,增加其体重及降低AchR抗体滴度。EAMG组胸腺中Caspase-3阳性细胞表达较对照组明显下调,耐受组其表达则明显增加,3组之间有显著的统计学意义(F=58.26,P<0.01)。结论 Rα97-116(V108A)鼻黏膜耐受能明显减轻EAMG大鼠肌无力症状,缓解胸腺细胞凋亡异常。In this study we investigate the effects of nasal immune tolerance on the apoptosis and caspase-3 expression of thymocytes in experimental autoimmune myasthenia gravis （EAMC） rats. Firstly, we randomly divided the rats into the control group, EAMG group and tolerance group. The rats of EAMG group and tolerance group were immunized with AchR ct 97-116 by muhipoint hypodermic injection. Subsequently, the rats of tolerance group were immunized with Rα 97-116 （V 108A） by the rout of nose. Ten days after, the clinical therapeutic effects （clinical symptom, weight, auti-AchR antibody titer） was evaluated; the positive apoptosis thymocyte of the three groups were assayed by TUNEL method; the caspase-3 positive cells in the thymus of the three groups were measured by immunohistochemistry methods. We found that the numbers of apoptosis thymocyte in EAMG group were lower than that of the control group and tolerance group, while nasal immune tolerance with R ct 97-116 （V 108A） could improve muscle weakness symptom, increase the body weight, and decrease serum auti-AchR antibody titer of tolerance group rats. The expression of caspase-3 in thymocytes of EAMG group was down-regulated, as compared with the control group anti tolerance group （F = 58.26,P 〈 0.01）. The results imply that nasal immune tolerance with Rα97-116α（V108A） could ameliorate muscle weakness symptoms of EAMG rats and can enhance the apoptosis thymocytes of the EAMG group.

关 键 词：重症肌无力 鼻黏膜耐受 细胞凋亡 CASPASE-3 

分 类 号：R746.1[医药卫生—神经病学与精神病学]