静脉注射 IL-19重组质粒对大鼠实验性自身免疫性心肌炎的治疗作用

摘要

[ ABSTRACT] AIM:To evaluate the effect of intravenous injecting plasmid encoding interleukin-19-IgG on exper-imental autoimmune myocarditis ( EAM) in rats.METHODS:Cardiac myosin was emulsified with equal volume of com-plete Freund’ s adjuvant.The animal model of EAM was established by injecting with the preparation in both footpads of the Lewis rats.The rats were intravenously injected with the plasmid encoding IL-19-IgG on day 6.Echocardiography was per-formed before the rats were sacrificed on day 17.The effect of IL-19-IgG plasmid injection was evaluated by measuring the heart weight/body weight, myocarditis area, relative expression levels of atrial natriuretic peptide ( ANP) and brain natri-uretic peptide (BNP) in the hearts.The mRNA expression levels of related cytokines including IL-18, IL-1β, IL-12p35 and IFN-γwere detected.RESULTS:The rats in model group showed significant myocardial damage and a decrease in the left ventricular functions.The rats in the treatment group injected with IL-19-IgG plasmid showed an improvement of the cardiac functions.The ratio of heart weight/body weight, the area of myocarditis and the mRNA levels of ANP and BNP were significantly lower in IL-19-IgG treatment group than those in model group.The mRNA levels of IL-18, IL-1β, IL-12p35 and IFN-γwere also significantly decreased in IL-19-IgG treatment group.CONCLUSION:Intravenous injection of plasmid encoding IL-19-IgG effectively prevents the development of the left ventricular remodeling and myocardial damage in EAM rats.%目的：评估静脉注射白细胞介素19（ interleukin-19，IL-19）重组质粒对大鼠实验性自身免疫性心肌炎（ experimental autoimmune myocarditis，EAM）的治疗作用。方法：将猪心室肌球蛋白与等体积完全弗氏免疫佐剂充分混匀后，双足皮下注射制作大鼠EAM模型，免疫后第6天应用静脉注射方法将IL-19重组质粒导入体内，第17天行心脏超声检查后处死大鼠，检测心脏重量与体重比值、病理学评估、心肌炎面积率；实时荧光定量PCR检测心衰标记物心房钠尿肽（ atrial natriuretic peptide，ANP）、脑钠尿肽（ brain natriuretic peptide，BNP）的表达水平，进一步检测心肌相关炎症因子IL-18、IL-1β、IL-12p35和IFN-γ的表达水平。结果：IL-19重组质粒导入组的大鼠心功能得到显著改善；心脏重量体重比、心肌炎面积率、ANP、BNP的表达均较模型组明显下降；相关炎症细胞因子的表达也显著降低。结论：应用静脉注射法进行IL-19重组质粒体内导入治疗，明显抑制大鼠实验性自身免疫性心肌炎的炎症反应，减轻了心肌损伤从而改善心功能。