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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。
Objective To investigate the effects of nasal mucosal tolerance on thymocyte apoptosis and Caspase-3 expression in experimental autoimmune myasthenia gravis (EAMG) in rats. Methods The experimental rats were randomly divided into normal control group, EAMG group and tolerated group. EAMG group and tolerated group were made into EAMG rat model by multi-point subcutaneous injection of Rα97-116 peptide. The rats in the control group were immunostained with Rα97-116 (V108A) via nasal instillation. The therapeutic effect (clinical symptoms, body weight, antibody titer, etc.) was evaluated after 10 days. TUNEL method was used to count the control group, EAMG group and tolerance The thymocyte apoptosis of the rats was observed. The expression of Caspase-3 in the thymus lymphocytes was detected by immunohistochemistry and the staining intensity of the positive cells was analyzed. Results The number of apoptotic thymocytes in EAMG group was significantly decreased compared with that in control group. Nasal mucosal tolerance treatment could significantly promote the apoptosis of thymocytes in EAMG rats and improve the symptoms of muscle weakness in EAMG rats, increase their body weight and decrease AchR Antibody titers. The expression of Caspase-3 positive cells in the thymus of EAMG group was significantly lower than that of the control group, but significantly increased in the tolerated group (F = 58.26, P <0.01). Conclusion Nasal mucosal tolerance of Rα97-116 (V108A) can significantly reduce the symptoms of myasthenia gravis in EAMG rats and relieve the abnormal apoptosis of thymocytes.