鼻黏膜耐受在实验性自身免疫性重症肌无力治疗中的作用

Treatment functions of nasal tolerance with dual analogue on experimental autoimmune myasthenia gravis in Lewis rats

目的 对实验性自身免疫性重症肌无力 (EAMG)动物模型采用双类似物进行鼻黏膜免疫耐受治疗 ,观察其临床及免疫功能的变化 ,评价临床疗效及探讨作用机制。方法 建立Lewis大鼠EAMG实验动物模型 ,检测致敏同时 (A组 )和缓解期第 1天 (B组 )给予双类似物鼻黏膜免疫耐受治疗后 ,大鼠的体重、临床症状、致敏第 4 2天血清抗AChR抗体IgG含量。结果 ①EAMG大鼠经其治疗后体重增加 ,临床症状得以缓解。②治疗后的血清抗AChR抗体IgG含量均少于各自对照组 ,A组少于B组 ,均有显著差异 (P <0 0 5 )。结论 双类似物鼻黏膜耐受治疗EAMG明显地缓解了肌无力症状 ,伴随特异性体液免疫功能的抑制 。

Objective To study the treatment functions of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG) and the underlying mechanisms, the clinical and immunological changes were observed in Lewis rats treated with dual analogue. Methods Different doses of dual analogues were given to Lewis rats immunized with acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA) and the medium dosage was chosen in the following studies. To compare the treatment effects of the predetermined dosage of dual analogue at different time points, the body weight and clinical symptoms of Lewis rats immunized with AChR in CFA were evaluated. The levels of anti-AChR IgG in serum were tested by RIA. Results Compared with the corresponding control groups, Lewis rats receiving dual analogue nasally for 10 consecutive days at the time of immunization (Group A) or the first day after complete remission from the acute phase of the disease (Group B) developed EAMG with reduced severity, and the subsiding disease was associated with decreased amount of anti-AChR IgG in serum expressed on the 42 day post immunization . Conclusions Nasal administration with a dual analogue, Lys 262-Ala 207, at two different time points post immunization ameliorated muscular weakness in EAMG rats associated with decreased levels of anti-AChR antibodies. Our results might give light to mucosal tolerance with dual analogue as an alternative maneuver in human MG.