阿托伐他汀抑制代谢综合征诱导的小鼠心脏重构

Atorvastatin inhibits mice cardiac remodeling induced by metabolic syndrome

目的探究阿托伐他汀(Atorvastatin,ATO)在高脂饮食(high fat diet,HFD)和N-硝基-L-精氨酸甲酯(Nnitro-L-arginine methyl ester,L-NAME)双打击诱导的小鼠代谢紊乱和心脏重构中的作用。方法采用HFD+LNAME构建代谢综合征诱导小鼠心脏重构模型。将C57BL/6J小鼠随机分为对照组(Chow)、模型组(HFD+LNAME+Vehicle)、10 mg·kg^(-1)·d^(-1) ATO组(HFD+L-NAME+ATO10)和20 mg·kg^(-1)·d^(-1) ATO组(HFD+L-NAME+ATO20),每组6只。监测各组小鼠空腹血糖、葡萄糖耐量试验、4项血脂水平、体重和血压的变化。造模12周后,通过心脏超声评估小鼠心功能改变。通过心脏病理切片HE染色观察小鼠心脏形态和室壁厚度改变,马松染色观察心脏纤维化程度改变,小麦胚芽凝集素(wheat germ agglutinin,WGA)免疫荧光观察心肌大小改变。通过Western blot检测小鼠心脏CollagenⅠ和α-SMA蛋白表达改变。结果与模型组比较,ATO可降低HFD+L-NAME诱导的小鼠空腹血糖升高(P=0.006,F=5.56),维持血糖和血脂稳态,同时抑制小鼠体重(P<0.001,F=11.75)和血压升高。心超结果显示,ATO改善HFD+L-NAME诱导的小鼠心排出量下降(P<0.001,F=23.56)。WGA和Western blot结果显示,ATO抑制HFD+L-NAME诱导的小鼠心脏室壁增厚(P<0.001,F=11.75)、纤维化增加(P=0.002,F=10.95)、心肌肥大(P<0.001,F=40.08)、CollagenⅠ(P=0.014,F=4.49)和α-SMA(P=0.004,F=6.28)蛋白表达升高。结论ATO改善HFD+L-NAME诱导的小鼠糖脂代谢异常、肥胖和高血压,抑制HFD+L-NAME诱导的小鼠心脏重构。

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(LNAME).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 CollagenⅠandα-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+LNAME 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),CollagenⅠ(P=0.014,F=4.49)andα-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.