CAI Jia-li, WANG Xia, YIN An-wen, SHEN Ye-jiao, XIAO Qing-qing, SHEN Ling-hong, HE Ben
Objective To investigate the role of Atorvastatin (ATO) in mice with metabolic disorders and cardiac remodeling induced by high fat diet (HFD) and N-nitro-L-arginine methyl ester (L-NAME). Methods HFD+L-NAME was used to construct the mice cardiac remodeling model induced by metabolic syndrome.C57BL/6 mice were randomly divided into the control group (Chow), the model group (HFD+L-NAME +Vehicle), the 10 mg·kg-1·d-1 ATO group (HFD+L-NAME+ATO10) and the mg·kg-1·d-1 ATO group (HFD+L-NAME+ATO20).The changes of fasting blood glucose, glucose tolerance test, blood lipid levels, body weight and blood pressure in mice were monitored.After 12 weeks of modeling, cardiac function of the mice was evaluated by Echo. HE staining was used to observe the changes of heart morphology and ventricular wall thickness, and Masson staining was used to observe the changes of cardiac fibrosis.The changes of myocardial size were observed by WGA immunofluorescence, and the protein expressions of Collagen Ⅰ and α-SMA were detected by Western blot. Results Compared with the model group, Atorvastatin reduced the HFD+L-NAME induced fasting glucose increase (P=0.006, F=5.56), maintained blood glucose and lipid homeostasis, and inhibited the increase of body weight (P<0.001, F=11.75) and blood pressure in mice.Echo results showed that Atorvastatin improved HFD+L-NAME induced the mice cardiac output reduction (P<0.001, F=23.56).The results of WGA and protein immunoblotting showed that Atorvastatin inhibited HFD+L-NAME induced cardiac wall thickness increased (P<0.001, F=11.75), myocardinal fibrosis increased (P=0.002, F=10.95), myocardial hypertrophy (P<0.001, F=40.08), Collagen Ⅰ (P=0.014, F=4.49) and α-SMA (P=0.004, F=6.28) protein expression increased in mice. Conclusion Atorvastatin improves the abnormal glucose and lipid metabolism, obesity and hypertension induced by HFD+L-NAME, and inhibits the cardiac remodeling induced by HFD+L-NAME in mice.
