目的：对实验性自身免疫性重症肌无力(EAMG)幼鼠选择双类似物（Lys262-Ala207）通过不同时间点进行鼻黏膜免疫耐受预防性给药后，观察其临床及免疫指标的变化，评价临床疗效及探讨鼻黏膜耐受对EAMG的预防作用机制。方法：用乙酰胆碱受体单克隆抗体建立C57BL/6小鼠EAMG模型，并在致敏前10 d(A组)及致敏当日(B组)经鼻黏膜滴入Lys262-Ala207诱导黏膜耐受，检测给药后A,B组及相应对照组CA组、CB组小鼠的临床症状及各项指标的改变情况。结果：①A，B两组临床症状明显轻于相应对照组,且A组临床症状轻于B组。②A，B组低频重复电刺激（RNS）出现衰减的阳性率低于各自对照组；③A，B两组小鼠血清乙酰胆碱受体抗体AchRAb(IgG)水平明显低于各自对照组，且A组轻于B组。④调节性CD4+CD25+T细胞含量A组（4.516±0.598）明显高于B组（3.671±0.300），且A，B组明显高于各自对照组。结论：Lys262-Ala207鼻黏膜预防耐受可有效地抑制重症肌无力的临床症状，为采用该途径治疗重症肌无力的可行性提供了理论依据。

OBJECTIVE: To study the prophylactic effects of nasal tolerance with a dual analogue, Lys262-Ala207, on the mouse model of experimental autoimmune myasthenia gravis (EAMG) and the underlying mechanism. METHODS: Mouse model of EAMG was induced by intraperitoneal injection of mAb35. Lys262-Ala207 or PBS was given nasally before 10 days (study group A and control group A) or on the day (study group B and control group B) of immunization for 10 days. Clinical syndromes were evaluated after immunization. Serum level of acetylcholine receptor antibody (AChR-Ab) IgG was detected using ELISA. The number of monouclear cells expressing CD4+ and CD4+ CD25+T from spleen was measured using flow cytometry. RESULTS: Compared with the corresponding control groups, the clinical syndromes were improved (P<0.01) in mice from the study groups A and B. The positive rate of the repetitive nerve stimulation (RNS) test in the study groups A and B was significantly lower than that in the corresponding control groups (P<0.01). The study group A showed lower positive rate of RNS than the study group B (P<0.05). The serum levels of AChR-Ab IgG in the study groups A and B (15.01±1.09 and 19.23±1.31 μg/mL) decreased compared with that in the corresponding control groups (28.12±1.28 and 29.35±1.28 μg/mL) (P<0.01). The study group A mice had lower serum AChR-Ab IgG levels than the study group B (P<0.01). The number of CD4+ CD25+T cells in the study groups A (4.516±0.598%) and B (3.671±0.300%) increased significantly compared with that in the corresponding control groups (2.661±0.411% and 2.412±0.500%) (P<0.01) and more CD4+ CD25+T cells were found in the study group A than in the study group B (P<0.01). CONCLUSIONS: Nasal administration with dual analogues may ameliorate clinical syndromes in EAMG rats, which may be associated with decreased serum AChR-Ab IgG levels and increased number of CD4+ CD25+T cells from spleen.