小鼠垂体中叶素对异丙肾上腺素诱导的小鼠心脏肥大的保护作用研究

Study on protective effects of mouse intermedin against isoproterenol induced cardiomegaly

目的利用异丙肾上腺素(ISO)诱导的小鼠心脏肥大模型研究小鼠垂体中叶素(IMD)拮抗心脏肥大的药理学作用和机制。方法建立小剂量ISO皮下注射诱导心脏肥大的小鼠模型,研究IMD给药后的小鼠血流动力学指标和心质量/体质量比,然后利用心脏组织切片评价心肌细胞横截面积、凋亡和纤维化。采用荧光实时定量PCR法检测心脏组织的心钠素(ANP)、脑钠肽(BNP)、内源性IMD及其受体系统的mRNA表达水平。结果与ISO诱导的小鼠心脏肥大模型组相比较,腹腔注射IMD治疗明显降低ISO处理所增加的心质量/体质量比和心肌细胞横截面积、心脏肥大标志物ANP及BNP的mRNA水平,以及心肌细胞凋亡率和心肌组织纤维化率。同时,改善心脏功能,左室压力、等容收缩期左心室内压力上升的最大和下降的最小速率、每搏排血量、心输出量和射血分数明显增加,而左心室舒张末期压力显著降低。此外,ISO处理明显诱导心脏组织内源性IMD及其受体的表达。结论 ISO诱导心脏组织内源性IMD及其受体的表达,外源性给与IMD治疗可能通过ISO活化的IMD受体系统实现其拮抗心脏肥大的药理学保护作用。

Objective To investigate the pharmacological effect and mechanism of mouse intermedin （IMD） for antagonizing cardiac hypertrophy by using isoproterenol （ISO） induced mouse cardiomegaly model. Methods The mouse cardiomegaly model was constructed by small dose of ISO subcutaneous injection. The mouse blood dynamic indexes and heart weight/body weight ratio were investigated. Then the cardiomyocyte cross-sectional area,apoptosis and cardiac tissue fibrosis were evaluated by using the cardiac tissue section. ANP,BNP,mRNA expression levels of endogenous IMD and its receptors system in cardiac tissues were detected by using real time fluorescence PCR method. Results Compared with the ISO induced mouse cardomegaly model group,the intraperitoneal injection of IMD significantly decreased the heart weight/ body weight ratio and cardiomyocyte cross-sectional area increased by ISO treatment, cardiomegaly marker ANP and BNP mRNA level, cardiomyocyte apoptosis and cardiomyocyte fibrosis, improved the cardiac function,left ventricular pressure,maximal and minimal rate of LV pressure increase and decrease during the isovolumetric contraction phase, stroke volume,cardiac output and ejection fraction, but significantly decreased the left ventricle enddiastolic pressure. In addition,the ISO treatment significantly induced the expressions of endogenous IMD and its receptors in heart tissues. Conclusion ISO induces the expressions of endogenous IMD and its receptors in cardiac tissues,and exogenous IMD supplementation therapy realizes the pharmacological protective effect for antagonizing cardiomegaly by ISO activated IMD receptor system.