福辛普利对胰岛素抵抗小鼠心室重构及脂联素表达的影响

Effect of fosinopril on ventricular remodeling and expression of APN in insulin resistant mice

目的:观察福辛普利干预对胰岛素抵抗(IR)小鼠心室重构及血清和心肌组织中脂联素(APN)表达的影响。方法:随机将40只C57BL/6野生型小鼠分为正常对照组、IR组、Fos7.5组和Fos15组,每组10只。正常对照组给予普通饲料喂养,其余3组均给予高脂饲料喂养,Fos7.5组和Fos15组同时每日分别给予福辛普利7.5mg-1·kg-1·d-1和15mg-1·kg-1·d-1灌胃,共喂养12周。测定体质量、空腹血糖(FPG)及空腹胰岛素(Fins),计算胰岛素抵抗指数(HOMA-IR);采用超声心动图检测左心室后壁厚度、室间隔厚度、左心室射血分数(LVEF)和左室短轴缩短率(LVFS),测定全心质量、左心室质量、左心室质量指数(LVWI);HE染色观察心肌结构微观改变;ELISA法测定血清转化生长因子-β1(TGF-β1)及APN水平,免疫组织化学和Western blot法测定心肌组织中TGF-β1及APN水平。结果:与正常对照组比较,IR组小鼠FPG、Fins及HOMA-IR均升高,左心室后壁厚度及室间隔厚度增加,LVEF和LVFS降低,体质量、全心质量、左心室质量增加,LVWI减小,心肌纤维断裂,排列紊乱,血清及心肌组织中TGF-β1表达升高,APN表达降低(均P<0.05)。与IR组比较,Fos7.5组和Fos15组FPG、Fins水平及HOMA-IR均降低,左心室后壁厚度及室间隔厚度均减小,LVEF和LVFS均升高,体质量、全心质量、左心室质量及LVWI均减少,心肌微观结构变化改善,血清及心肌组织中TGF-β1表达降低,APN表达升高,且Fos15组效果更显著(均P<0.05)。结论:IR小鼠存在明显心室重构。福辛普利可改善IR小鼠心室重构,且呈剂量依赖性,这种作用可能与APN表达升高有关。

Objective：To observe the effect of fosinopril（Fos）on ventricular remodeling and expression of adiponectin（APN）in insulin resistant（IR）mice.Method：Forty C57BL/6wild type mice were randomly divided into normal control group,IR group,Fos7.5group and Fos15 group,with 10 mices in each group.The control group was given normal diet,the other three groups were fed with high fat diet,meanwhile,Fos7.5group（7.5mg^-1·kg^-1·d^-1）and Fos15group（15mg^-1·kg^-1·d^-1）were gave with fosinopril every day for 12 weeks.The body weight,fasting plasma glucose（FPG）and fasting insulin（Fins）were measured,then the insulin resistance index（HOMA-IR）was calculated.Left ventricular posterior wall thickness,ventricular septalthickness,left ventricular ejection fraction（LVEF）and left ventricular fractional shortening（LVFS）were detected with echocardiography.The whole heart weight,left ventricular weight,left ventricular mass index（LVWI）were measured.HE staining was used to observe the myocardial micro change.ELISA was used to detect TGF-β1and APN level in serum.The expressions of TGF-β1and APN in cardiac muscle tissue were measured by immunohistochemistry and Western blot.Result：Compared with the control group,FPG,Fins and HOMA-IR,left ventricular posterior wallthickness and ventricular septum thickness were increased,while LVEF,LVFS,body weight,heart weight,left ventricular weight,LVWI were decreased,the myocardial fibers were broken and arranged in disorder,the levels of APN in serum and myocardial tissues were decreased,TGF-β1were increased in IR group（all P〈0.05）.Compared with the IR group,FPG,Fins and HOMA-IR were significantly decreased in Fos7.5group and Fos15 group,and left ventricular wall thickness and ventricular septal thickness were decreased,LVEF and LVFS were increased,body weight,heart weight,left ventricular weight and LVWI were decreased.Myocardial microstructure had been improved,the level of APN in serum and myocardial tissue were increased,TGF-β1were decreased in the two Fos groups,and the effect of changes was more significant in Fos15group（P〈0.05）.Conclusion：IR mice are accompanied by obvious ventricular remodeling.Fosinopril can improve the ventricular remodeling in IR mice with dose dependent.The effect may be associated with elevated of expression of APN.