Effect Of Fosinopril To Expression Of Adiponectin And Ventricular Remodeling In Insulin Resistant Mice

Objective The aim of this study was to observe the effect of fosinopril(Fos)to expression of adiponectin(APN),Adipo R1 and ventricular remodeling in insulin resistant(IR)mice.Method: 50 C57BL/6 wild type mice were randomly divided into normal control group,IR group,Fos7.5 group,Fos15 group and Fos30 group,with 10 mices in each group.The control group was given normal diet,the other groups were fed with high fat diet,meanwhile,Fos7.5 group,Fos15 group and Fos30 group were gavaged with fosinopril every day for 12 weeks.We measured body weight,fasting blood glucose and fasting insulin,then calculated insulin resistance index.Left ventricular posterior wall thickness,ventricular septal thickness,LVEF and LVFS were detected with echocardiography.We measured whole heart weight,left ventricular weight,then calculated left ventricular mass index(LVWI).Morphological changes of myocardial cells were observed by HE staining.ELISA was used to detect TGF-β1 and APN level in serum.TUNEL method was used to detect the apoptosis rate of myocardial cells.The expression of TGF-1,APN and Adipo R1 in myocardial tissue were determined by immunohistochemistry and Western blot.PCR was used to detect APN and Adipo R1 m RNA expression in myocardium.Result:(1)Compared with the control group,fasting blood glucose,fasting insulin and HOMA-IR increased,left ventricular posterior wall thickness and ventricular septum thickness were increased in IR group,while LVEF and LVFS,body weight,heart weight,left ventricular weight,left ventricular weight index were decreased,the myocardial fibers were obviously broken,arranged in disorder,the size of nuclei was different,and the apoptosis rate of myocardial cells was obviously increased.The level of TGF-beta 1 protein in serum was increased and the level of APN protein was decreased.The expression of TGFbeta protein was increased,the expression of APN and Adipo R1 protein was decreased,and the expression of APN and Adipo R1 were decreased in the myocardial tissue of m RNA(P<0.05).(2)Compared with the IR group,fasting blood glucose,fasting insulin and HOMA-IR were significantly decreased in Fos7.5 group,Fos15 group and Fos30 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 left ventricular weight index were decreased.The myocardial fiber breakage was improved,the arrangement was more orderly,the cell size was uniform,and the apoptosis rate of myocardial cells was improved obviously.The level of serum TGF-beta 1 protein was decreased,the APN protein level was increased,the expression of TGF-beta 1 protein was decreased,the expression of APN and Adipo R1 protein was increased in the myocardial tissue,and the expression of APN and m RNA was increased in Adipo R1.With the increase of the dose of Phu Simpson Leigh intervention,the observation effect was more significant(P<0.05).Conclusion: High fat diet can induce insulin resistance,insulin resistance in mice can increase the apoptosis of myocardial cells,and the presence of ventricular remodeling.Fosinopril can improve insulin resistance,reduce myocardial cell apoptosis and prevent and inhibit ventricular remodeling,which may be related to the increased expression of APN and Adipo R1.In a dose-dependent manner.