双类似物鼻黏膜耐受在EAMG发病中的预防作用机制  

The Mechanism of Prophylactic Effects of Nasal Tolerance with Dual Analogue on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

作　　者：王化冰[1] 王丽华 富羽弘[1] 王维治[1] 

机构地区：[1]哈尔滨医科大学附属第二医院神经科,黑龙江哈尔滨150086 [2]解放军211医院急诊科,黑龙江哈尔滨150080

出　　处：《中国神经免疫学和神经病学杂志》2004年第1期4-8,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目 (3 9970 2 62 )

摘　　要：目的　采用双类似物 (Lys2 62 -Ala2 0 7)对实验性自身免疫性重症肌无力 (EAMG)模型进行鼻黏膜耐受不同时间点预防性给药 ,观察临床及免疫指标变化 ,以探讨其对 EAMG免疫发病中的预防作用机制。方法　应用乙酰胆碱受体 (ACh R)加福 (氏 )佐剂致敏 Lewis大鼠建立 EAMG模型 ,在致敏前 1 0 d(预防耐受 A组 )及致敏当日 (预防耐受 B组 )经鼻腔给药 ,评价给药后 A、B组及对照组大鼠体重、临床症状 ,观察肌电图变化、检测致敏第 42天血清抗 ACh R抗体 Ig G及其亚型含量和第 5 0天处死后淋巴结单个核细胞 (MNC)中 IFN-γ、IL-4及 IL-1 0分泌细胞含量变化。结果　 (1 )急性期和慢性期 A、B组体重增加而临床症状明显轻于对照组 ,慢性期 A组临床症状轻于 B组 ;(2 ) A、B组低频重复电刺激出现明显衰减的阳性率低于对照组 ;(3 )慢性期 A、B组 Ig G含量明显低于对照组 ,且 A组低于 B组 ,各组间抗体亚型 Ig G1含量无明显差异 ,而 A、B组的 Ig G2 a和 Ig G2 b含量明显少于各自对照组 ,B组 Ig G2 b含量高于 A组 ;(4 ) A、B组淋巴结中的 IFN-γ、IL-4及 IL-1 0阳性细胞含量均明显低于各自对照组。结论　Lys2 62 -Ala2 0 7鼻黏膜预防耐受不仅可有效地抑制临床症状 ,并使致病性最强的ACh R特异性 Ig G2抗体分泌量减少 ,IgObjective To study the prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG) and the underlying mechanisms. Methods To compare the effects of the predetermined dosage of Lys262-Ala207 at different time points, dual analogues and control peptides were given nasally before (Group A or CA) or on the day (Group B or CB) of immunization with acetylcholine receptor (AChR) in complete Freud's adjuvant(CFA) for 10 consecutive days. The clinical scores were evaluated for 50 days post immunization. The levels of anti-AChR IgG and IgG isotype in serum were tested by ELISA.The numbers of MNCexpressingIFN-γ, IL-4 orIL-10fromlymphnodeswere enumerated by flow cytometry. Results Group A and group B of Lewis rats developed EAMG with reduced severity and decremental CAMP as compared to the corresponding control groups. The levels of anti-AChR IgG, IgG2a and IgG2b, but not IgG1 were decreased. The contents of cells synthesizing IFN-γ, IL-4 or IL-10 were lower in group A and B than their corresponding control groups. Conclusions Nasal administration with a dual analogue Lys262-Ala207, at two different time points before and on the day of immunization ameliorated muscular weakness in EAMG rats associated with decreased levels of anti-AChR IgG, IgG2a and IgG2b in serum, a reduced percentage of cells synthesizing IFN-γ, IL-4orIL-10in group A and B as compared to rats receiving control peptides. However, these results might give light to mucosal tolerance with dual analogue as an alternative treatment in human MG.

关 键 词：自身免疫性重症肌无力 鼻黏膜 耐受 双类似物 作用机制 动物模型 乙酰胆碱受体 细胞因子 

分 类 号：R746.1[医药卫生—神经病学与精神病学]