【摘要】 目的:评估编码Ⅱ型白细胞介素-1受体（typeⅡinterleukin-1 receptor,IL-1RⅡ）的重组质粒在大鼠实验性自身免疫性心肌炎（experimental autoimmune myocarditis,EAM）中的治疗效果。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,于第0 d Lewis大鼠双后足皮下注射制作EAM模型,第6 d应用流体动力学方法进行重组质粒IL-1RⅡ的体内导入,第17 d进行大鼠心脏超声检查后,处死大鼠,检测大鼠心/体重比值、心脏病理学评估及心肌炎面积率,进一步应用实时荧光定量RT-PCR检测心衰标记物脑钠尿肽（brain natri-uretic peptide,BNP）的水平。同时检测白细胞介素-1（interleukin-1,IL-1）相关因子白细胞介素-1β（interleukin-1 beta,IL-1β）、前列腺素E₂合成酶（prostaglandin E₂ synthase,PGES）以及单核细胞趋化蛋白-1（monocytechemotactic protein-1,MCP-1）mRNA及蛋白表达水平。结果:IL-IRⅡ重组质粒导入后次日表达量最高,且升高持续实验整个过程至第17 d。IL-1RⅡ治疗组的大鼠心/体重比值、心肌炎面积率、BNP及IL-1表达均较对照组有明显下降,大鼠左室心功能亦有明显改善。结论:应用流体动力学方法进行重组质粒IL-1RⅡ的体内导入治疗,对大鼠实验性自身免疫性心肌炎有改善左室功能和阻止心肌损害作用。更多还原

【Abstract】 ADM:To evaluate the effect of gene delivery plasmid encoding interleukin-1 receptorⅡ（IL-1RⅡ） for treating rat experimental autoimmune myocarditis（EAM ）.METHODS:Cardiac myosin was emulsified with equal volume of complete Freund’s adjuvant,and EAM model was produced by injection with the preparation in both footpads of Lewis rats.The rats were immunized on day 0 and were injected with plasmid encoding IL-1RⅡby hydrodynamicsbased gene delivery on day 6.The expression of IL-1RⅡon day 7,day 12 and day 17 was determined by Western blotting. Echocardiography was performed on day 16 and the rats were sacrificed on day 17.The effect of IL-1R II gene therapy was evaluated by the ratio of heart weight/body weight,histopathological scores,relative expression of brain natriuretic peptide（BNP） in hearts and the echocardiographic parameters.The expression levels of IL-1 -related cytokines,including IL-1β,prostaglandin E₂ synthase（PGES） and monocyte chemotactic protein-1（MCP-1 ） were also detected. RESULTS:The expression of IL-1RⅡincreased on day 7 after hydrodynamics-based gene delivery and maintained at high level until day 17.The rats in control group showed significant myocardial damage and a decrease in the left ventricular functions. The rats in the treatment group injected with IL-1RⅡplasmid showed an improvement of the cardiac functions. The ratio of heart weight/body weight,the histopathological scores and the level of BNP were significandy lower in treatment group than those in control group.The expression of IL-1β,PGES and MCP-1 at mRNA and protein levels was also significantly inhibited in IL -1RⅡtreatment group.CONCLUSION:Hydrodynamics-based gene delivery plasmid encoding IL -1RⅡeffectively prevents the progression of the left ventricular remodeling and myocardial damage in rat EAM.更多还原