ISO和AngⅡ诱导小鼠心脏纤维化模型的表型及机制比较

Comparison of Phenotype and Signal Pathway in Experimental Mouse Models of Cardiac Fibrosis Induced by ISO and AngⅡ

该文旨在比较异丙肾上腺素(isoprenaline,ISO)和血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)诱导的2种小鼠心脏纤维化模型在心功能、心肌纤维化及发生机制等方面的差别。采用C57野生型小鼠随机分为ISO组、AngⅡ组和生理盐水对照组。在背部皮下植入AngⅡ微量泵或者皮下注射ISO,28天后比较各组的心功能、静脉压、心重指数(cardiac weight index,CWI)、心肌组织纤维化程度和纤维化分子表达差异,以及信号通路改变情况。结果显示,ISO组和AngⅡ组在心功能受损方面无显著差异,而在静脉压、CWI方面ISO组都低于AngⅡ组,在心肌组织纤维化程度和纤维化分子表达水平方面,ISO组都高于AngⅡ组。两种模型中纤维化发生的信号通路机制也明显差异。因此,该实验结果表明,ISO模型通过不同于AngⅡ模型的信号通路机制来诱导更为显著的心肌纤维化病理改变。

The aim of the study was to critically evaluate the available evidence regarding the difference between mouse models of cardiac fibrosis induced by ISO(isoprenaline)and AngⅡ(angiotensin Ⅱ).C57 wild type mice were randomly divided into ISO group,AngⅡ group and NS(normal saline)control group.Mice in ISO model group were given subcutaneous injection of ISO.Mice in AngⅡ model group were treated with AngⅡ infusion via an implanted osmotic minipump.The mice of control group were administered normal saline in the same way.After 28 days,cardiac function and fibrosis were evaluated by echocardiography,micromanometry,histology and CWI(cardiac weight index).The results showed that there were no difference in cardiac function between ISO and AngⅡ models in terms of cardiac function.However,mice receiving ISO displayed more severe cardiac fibrosis,lower vein systolic pressure and CWI compared with mice receiving AngⅡ.Importantly,the different signaling pathways activated in the two models were found.These findings indicate that pathological change of cardiac fibrosis induced by ISO model is severer than that in AngⅡ model through different signaling pathway.