摘要
目的 用双类似物鼻黏膜耐受治疗实验性自身免疫性重症肌无力 ( EAMG)大鼠 ,探讨其对机体免疫机制的影响。方法 建立 Lewis大鼠的 EAMG模型 ,在致敏同时 ( A组 )及缓解期第 1天 ( B组 )给予双类似物 3 0 0μg/只。动态评估大鼠临床症状 ,检测外周血 ( PB) ACh R-Ab( Ig G)含量 ,检测急、慢性期 PB单个核细胞 ( MNC)及致敏第 5 0天淋巴结、脾 MNC中的 CD4+ CD2 5 + 细胞数改变。结果 治疗组大鼠临床症状减轻 ;治疗组及对照组大鼠 PB中特异性 ACh R-Ab( Ig G)含量随病程延续而增加 ,但在致敏后第 5及第 7周 ,A、B组特异性 Ig G抗体含量比各自对照组显著减低 ( P <0 .0 5 ) ;双类似物鼻黏膜耐受治疗后 ,EAMG大鼠 PB MNC中的 CD4+ 细胞数减少 ( P<0 .0 5 ) ,CD4+ CD2 5 +细胞数相对增加 ( P<0 .0 5 ) ;A、B组淋巴结和脾 MNC中 CD4+细胞数减少( P<0 .0 5 ) ,CD4+ CD2 5 +细胞数只在 B组相对增加 ( P <0 .0 5 )。结论 双类似物鼻黏膜耐受治疗病情进展中的 EAMG有效 ;伴随临床症状缓解 ,治疗组大鼠 ACh R-Ab( Ig G)含量减少且免疫调节性 CD4+ CD2 5 +细胞数相对增多 ;双类似物治疗 EAMG的可行性为抗原特异性治疗重症肌无力 ( MG)和其他自身免疫性疾病 ( AID)提供了依据。
Objective To study the therapeutic effect of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG) and to elucidate the underlying immune mechanism, in Lewis rats treated with dual analogue. Methods 300 μg/rat of dual analogues was given to Lewis rats immunized with acetylcholine receptor (AChR) in complete Freund adjuvant(CFA) at two different time points and the clinical symptoms were evaluated. Then the amount of anti-AChR IgG in serum were tested by ELISA, while the numbers of CD4+ CD25+ cells from blood, lymphocyte and spleen were tested by flow cytometry. Results Lewis rats receiving dual analogue nasally for 10 consecutive days at the time of immuniza-tion or on the first day after complete remission from acute phase of the disease developed EAMG all were with reduced severity. Compared with their respective control groups, the group A and group B had decreased amount of anti-AChR IgG in the 5th and 7th weeks.While the absolute reduction of CD4 T cells (P<0.05) and relatively increased numbers of CD4+ CD25+ cells from blood (P<0.05), lymph node and spleen (P<0.05) were observed. Conclusions Nasal tolerance induced by a dual analogue Lys-262-Ala-207 can treat clinical EAMG and modulate the immune function of EAMG rats. This gives light to mucosal administration of dual analogue as an alternative maneuver in human myasthenia gravis (MG).
出处
《中国神经免疫学和神经病学杂志》
CAS
2003年第3期197-200,207,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)