The Effect And Mechanism Of Atorvastatin On Ventricular Remodeling In Insulin Resistant Mice

ObjectiveTo investigate the effect and mechanism of atorvastatin on ventricular remodeling in insulin resistance（IR）mice.Methods40 C57BL/6 wild-type male mice were divided into 4 groups by random number table:normal control group（Control group）,IR group,Ato10 group and Ato20 group with 10 rats in each group.The Control group was fed with normal diet,the other three groups were fed with high-fat diet.The Ato10 group(10mg^-1·kg-1·d^-1)and the Ato20 group(20mg^-1·kg-1·d^-1)were given atorvastatin every day for 12 weeks.Weighing mouse body weight;Fasting blood glucose（FPG）was measured;Serum fasting insulin（Fins）,APN and the receptor Adiponectin 1 were detected by ELISA;Left ventricular posterior wall thickness（LVPWd）,interventricular septal thickness（IVSd）,left ventricular ejection fraction（LVEF）,and left ventricular short axis shortening rate（LVFS）were measured by echocardiography;The weigh of the whole heart t and the left ventricular were measured.Detection of apoptosis rate by TUNEL method.HE staining was used to observe the changes of myocardial tissue structure in mice;The expression levels of APN and TGF-β1 and AdipoR1 in myocardium were detected by immunohistochemistry and Western blot.Results Echocardiography showed that LVPWd and IVSd were significantly increasedand,while LVEF and LVFS were significantly decreased in IR group（P<0.05）;FPG,Fins and HOMA-IR were significantly higher than the Control group（P<0.05）;The expression of APN in serum and myocardial tissue decreased significantly,and the expression of TGF-β1was significantly increased（P<0.05）;Body weight,whole heart weight and left ventricular mass were significantly increased（P<0.05）,of which LVWI showed a downward trend but was not obvious;It was found that the apoptosis rate of cardiomyocytes increased significantly;HE staining showed that the arrangement of myocardial cells was disordered,the morphology of the nucleus was different,and the muscle fibers were distorted and fractured;After different doses of atorvastatin treatment,the above indicators were improved compared,and the improvement effect was more significant in the group of 20mg（P<0.05）.ConclusionIR can cause ventricular remodeling in mice,and atorvastatin can improve IR-induced ventricular remodeling and the Ato20 group is better,suggesting that its mechanism may be related to decreased expression of TGF-β1 and elevated of expression of APN.