腺病毒介导反义CⅡTA基因对实验性自身免疫性心肌炎的治疗

Adenovirus-mediated gene transfer of antisense CⅡTA ameliorates ongoing experimental autoimmune myocarditis

目的 研究反义CⅡTA基因对心肌肌凝蛋白诱导的实验性自身免疫性心肌炎 (experi mentalautoimmunemyocarditis,EAM)的治疗作用。方法 以携带反义CⅡTA基因的腺病毒载体对肌凝蛋白免疫后的小鼠进行静脉注射 ,同时设立空载病毒组与单纯免疫组作为对照 ,以多种手段观察反义CⅡTA基因对EAM的治疗效果。结果 治疗组与两对照组相比 ,心肌病理损伤程度减轻 ;血浆抗心肌肌凝蛋白抗体滴度及cTnⅠ浓度明显下降 (P <0 .0 5 ) ,流式细胞术检测外周血与脾脏T细胞I Ad表达量明显下降 (P <0 .0 5 )。结论 反义CⅡTA基因对心肌肌凝蛋白诱导的EAM具有较好的治疗作用。

Objective To study the amelioration of experimental autoimmune myocarditis (EAM) in BALB/c mice after immunosuppression by adenovirus-mediated gene transfer of antisense CⅡTA. Methods EAM mice with or without treatment of antisense CⅡTA gene mediated by adenovirus were sacrificed on day 21 after first immunization with myosin from porcine heart. Heart pathology grading, concentration of cTnⅠ, titer of auto-antibody and cell phenotype in spleen and peripheral blood were compared among various groups as CⅡTA therapy(CT), simple immune(SI), GFP control(GC) and normal control(NC). Results Pathological and serological evaluation showed significant amelioration of EAM in CT group as compared with SI and GC groups (P<0.05). There is no difference in I-Ad expression on CD3- cells, but the difference is significant on CD3+ cells derived from spleen and peripheral blood(P<0.05). Conclusion The antisense CⅡTA gene mediated by adenovirus can effectively suppress autoimmune response in vivo and ameliorate EAM induced by porcine heart myosin.