外源性补充酮体对肥胖小鼠心肌线粒体功能及氧化应激的影响

Effects of Exogenous Ketone Body Supplementation on Myocardial Mitochondrial Function and Oxidative Stress in Obese Mice

目的探讨外源性补充酮体对肥胖小鼠线粒体功能及氧化应激的影响。方法采用随机分组对照研究的方法,将C57BL/6J雄性小鼠给予普通饲料或高脂饲料喂养。12周后,除普通饲料喂养的对照组,高脂饲料喂养的小鼠随机分为模型组和酮脂灌胃组。酮脂灌胃组使用酮脂灌胃4周,对照组和模型组用相同体积0.9%NaCl溶液灌胃。统计固定时间点小鼠体质量及血糖变化,采用经皮心脏超声检测小鼠心功能,检测氧化应激相关指标,脂质过氧化终产物丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活性及蛋白过氧化水平;使用Seahorse能量分析仪测定线粒体呼吸能力。结果与对照组比较,模型组小鼠体质量增长显著;葡萄糖耐受能力明显降低;左心室射血分数和左心室短轴缩短率均下降;心肌线粒体功能受损,体现在基础呼吸和最大呼吸均显著下降。心肌组织MDA含量明显增加、SOD活性大幅降低以及蛋白质过氧化水平加深。与模型组比较,酮脂灌胃后的肥胖小鼠心肌线粒体基础呼吸和最大呼吸均增高,MDA含量有所下降,SOD活性提高,同时蛋白过氧化水平下降。结论高脂饮食喂养诱导小鼠肥胖表型,伴随心脏线粒体功能损害及氧化应激增强,外源性补充酮体可以减轻肥胖小鼠心肌线粒体损伤,改善心脏氧化应激。

Objective To investigate the effects of exogenous ketone body supplementation on mitochondrial function and oxidative stress in obese mice.Methods C57BL/6J male mice were fed chow diet or high fat diet in a randomized controlled study.After 12 weeks,except for the control group fed with chow diet,the mice fed with high fat diet were randomly divided into model group and ketone ester intragastric group.Ketone ester was administered in gavage for 4 weeks,and the control group and model group were given the same volume of normal saline in gavage.The changes of body weight and blood glucose in mice at fixed time points were analyzed.Percutaneous cardiac ultrasound was used to detect the cardiac function of mice.The content of malondialdehyde(MDA),the activity of superoxide dismutase(SOD)and the level of protein peroxidation were detected as markers of oxidative stress.Mitochondrial respiratory capacity was measured by a seahorse energy analyzer.Results Compared with the control group,the weight of mice in model group increased significantly.Glucose tolerance was significantly reduced.The left ventricular ejection fraction and left ventricular short-axis shortening rate decreased.The function of myocardial mitochondria was impaired,which was reflected in the significant decrease of basal respiration and maximal respiration.MDA content increased significantly,SOD activity decreased significantly and protein peroxidation level deepened.Compared with the model group,the basic and maximum respiration of myocardial mitochondria of obese mice were increased,MDA content was decreased,SOD activity was increased,and protein peroxidation level was decreased.Conclusion High-fat diet induced the obesity phenotype of mice,accompanied by the impairment of cardiac mitochondrial function and the enhancement of oxidative stress.Exogenous ketone body supplementation could reduce the myocardial mitochondrial damage and improve cardiac oxidative stress in obese mice.