鼻粘膜耐受对实验性重症肌无力大鼠胸腺Fas、BCL-2表达的影响  

The role of nasal immune tolerance on the expression of Fas and Bcl-2 in the thymus of experimental autoimmune myasthenia gravis rats

作　　者：熊小平[1] 任明山[1] 杨毅[1] 许文华[1] 王晓秋[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]安徽医科大学附属省立医院病理科,合肥230001

出　　处：《中国神经精神疾病杂志》2009年第1期11-14,共4页Chinese Journal of Nervous and Mental Diseases

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：目的探讨实验性重症肌无力大鼠经鼻粘膜耐受处理后胸腺淋巴细胞Fas及BCL-2的表达及其免疫耐受的发生机制。方法将实验大鼠随机分为对照组、EAMG组及耐受组。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,并采用TUNEL法计数对照组、EAMG组及耐受组大鼠胸腺淋巴细胞阳性凋亡细胞数和免疫组化法检测3组大鼠胸腺淋巴细胞FAS及BCL-2的表达。结果Rα97-116(V108A)鼻粘膜耐受处理能明显改善EAMG大鼠的肌无力症状,增加其体重及降低AChR抗体滴度。EAMG组大鼠胸腺凋亡细胞数较对照组显著减少,而耐受组大鼠则较EAMG组明显增加,3组间差异具有显著的统计学意义(F=114.15,P<0.01)。3组大鼠胸腺细胞FAS的表达也具有统计学差异性(2=16.48,P<0.05),EAMG组大鼠胸腺细胞FAS表达较对照组显著下调,而耐受组表达增加。EAMG组胸腺细胞中BCL-2高表达,而耐受组表达量下降,3组之间存在统计学差异(2=15.82,P<0.05)。结论Rα97-116(V108A)鼻粘膜耐受能明显减轻EAMG大鼠肌无力症状,其自身反应性淋巴细胞的凋亡可能与鼻粘膜耐受的作用机制有关。Objective To investigate the effect of nasal immune tolerance on expression of Fas and Bcl-2 in thymus of experimental autoimmune myasthenia gravis（EAMG） rats. Methods The rats were randomly divided into EAMG, control and tolerance groups, the rat models of EAMG and the nasal tolerance were created by muh-spot subcutaneous injection of AchRα97-116（Rα97-116） , followed by immunization with Rα97-116（V108A） for EAMG or PBS for nasal tolerance for 10 days by the rout of nose, respectively. The therapeutic effect, positive apoptotic thymocyte the expressions of Fas and Bcl-2 in the thymus were evaluated. Results Compared with the EAMG group, nasal tolerance significantly attenuated body weight loss and muscle weakness symptom as well as decreased serum anti-AchR antibody titers. There were fewer apoptotic thymocyte in EAMG group than in control and tolerance groups （P 〈 0. 01 ）. Contrary to the expression of Bcl-2, the expression of Fas was lower in in the thymus of EAMG group than in control and tolerance groups （ P 〈 0. 05 ）. Conclusions Nasal mucous tolerance with Rα97-116（ V108A）could ameliorate muscle weakness symptoms of EAMG rats. The apoptosis of auto-reactive lymphocyte might be related to nasal immune tolerance. [ Key words ]

关 键 词：重症肌无力 鼻粘膜耐受 细胞凋亡 FAS Bcl-2 

分 类 号：R746.1[医药卫生—神经病学与精神病学]