Dual APL对EAMG免疫治疗时临床症状、黏附分子及趋化因子的影响  

Effects of dual altered peptide ligand on clinical symptoms,adhesion molecule and chemotatic factor in immunotherapy of experimental autoimmune myasthenia gravis

作　　者：王爽[1] 包忠蕾[1] 张丽梅[1] 闫晓波[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150081

出　　处：《哈尔滨医科大学学报》2012年第5期420-423,共4页Journal of Harbin Medical University

基　　金：黑龙江省自然科学基金资助项目(D200501);黑龙江省教育厅课题(11511145);黑龙江省卫生厅课题(2011-076);黑龙江省青年科学基金(QC2011C130)

摘　　要：目的探讨双修饰性多肽配体(dual altered peptide ligand,dual APL)对实验性重症肌无力(ex-perimental autoimmune myastheia gravis,EAMG)鼻黏膜免疫耐受时临床症状的影响,以及黏附分子及趋化因子在EAMG鼻黏膜免疫致病耐受机制中的作用。方法用AChR-α肽段P259-271联合白细胞介素12(interleukin-12,IL-12)建立EAMG鼠模型,将模型鼠随机分为干预组(经鼻黏膜给予dual APL,n=13)和模型组(经鼻黏膜给予生理盐水,n=13),进行临床评分、重复神经电刺激、光镜下观察dual APL免疫干预后胸腺增生情况及电镜下神经肌肉接头突触后膜损害程度,用ELISA法检测细胞间黏附分子-1(in-tercellular adhesion molecule-1,ICAM-1)及趋化因子-10(interferon inducible protein-10,IP-10)的表达。结果①dual APL免疫干预后可诱导鼻黏膜免疫耐受使临床症状减轻。②模型组鼠胸腺增生可见胸腺小体;模型组突出后膜皱褶数较干预组减少。③干预组黏附分子ICAM-1表达[(189.8±146.7)U/mL]较模型组[(547.3±251.4)U/mL)]减低(P<0.05);④干预组体内IP-10水平[(0.79±0.32)pg/mL]较模型组[(6.08±1.57)pg/mL]降低(P<0.01);干预组T细胞趋化数30 min[(5.3±0.3)×103/mL]、60min[(5.1±0.5)×103/mL]、90 min[(7.4±1.3)×103/mL]较模型组[(17.3±5.3)×103/mL、(20.0±6.7)×103/mL、(28.0±4.0)×103/mL]明显减少(P均<0.01),两组T细胞趋化数均在90 min达高峰。结论 dual APL能改善临床症状并可能具有抑制特异性T细胞与血管内皮细胞的黏附及趋化功能。Objective To explore the effects of dual altered peptide ligand（APL） on clinical symptoms,intercellular adhesion molecular-1 and interferon inducible protein-10（IP-10） in experimental autoimmune myasthenia gravis（EAMG） with nasal mucosa.Methods EAMG mice models were established by P259-271（AChR-α peptide） and IL-12.EAMG mice models were randomly divided into two groups： the experimental group（dual APL was given by nasal mucosa, n=13）;the model group（phosphate buffered solution was given by nasal mucosa,n=13）.The clinical scores,repetitive nerve stimulation,thymus hyperplasia under optical microscope and the extent of damage of postsynaptic membrane in neuromuscular junction under the electron microscope were detected.The expressions of ICAM-1 and IP-10 were detected by ELISA.Results ①The clinical symptoms were relieved in the experimental group.②Thymus hyperplasia was seen in the model group.The numbers of postsynaptic membrane reductus in the model group were less than that in the experimental group.③The expression levels of ICAM-1 in the experimental group[（189.8±146.7）U/mL]were lower than those in the model group [（547.3±251.4）U/mL）]（P0.05）;④The levels of IP-10 in the experimental group[（0.79±0.32）pg/mL] were lower than those in the model group[（6.08±1.57）pg/mL]（P0.01）;The numbers of T-cell chemotaxis in the experimental group were significantly lower than that in the model group at 30 min[（5.3±0.3）vs（17.3±5.3）×103/mL],60 min[（5.1±0.5）vs（20.0±6.7）×103/mL],90 min[（7.4±1.3）vs（28.0±4.0）×103/mL],P0.01.The numbers of T-cell chemotaxis increased to peak in both groups at 90 min.Conclusion dual APL may lighten the clinical symptoms,inhibit the functions of intercellular adhesion molecular and chemotaxis of the specific T-cells.

关 键 词：重症肌无力 自身免疫性 双修饰性多肽配体 鼻黏膜耐受 

分 类 号：R746.1[医药卫生—神经病学与精神病学]