长期高脂饮食对小鼠心肌组织自噬、凋亡及炎性反应的影响

Effects of long-term high-fat diet on autophagy, apoptosis and inflammation in myocardium of mice

目的:研究长期高脂饮食对小鼠心肌组织自噬、凋亡及炎性反应的影响。方法:6周龄雄性C57BL/6小鼠随机分为对照组和高脂喂养组,饲养至24周时,称量体质量,取小鼠心脏及附睾周围脂肪组织并称重,计算心脏质量/体质量比值;Western blot和实时荧光定量聚合酶链反应检测小鼠心肌组织自噬、心肌凋亡及炎性反应相关基因的mRNA和蛋白表达水平。结果:与对照组相比,高脂喂养组体质量、内脏脂肪和心脏组织质量均明显增加,心脏质量/体质量的比值也明显增加(P均<0.05);小鼠心肌组织自噬标志基因LC3Ⅱ的mRNA和蛋白表达明显降低,自噬核心基因Becn1的mRNA和蛋白表达水平也明显降低(P均<0.05);凋亡相关基因Bax和Bad的mRNA表达水平均明显升高,凋亡标志蛋白裂解型胱天蛋白酶-3(c-caspase-3)和裂解型多聚腺苷二磷酸核糖聚合酶(c-PARP)的蛋白表达水平均明显升高(P均<0.05);炎性基因NLRP3、白细胞介素(IL)-1β和胱天蛋白酶-1(caspase-1)的mRNA表达水平均明显增加(P均<0.05)。结论:长期高脂饮食抑制小鼠心肌组织自噬,增加心肌细胞凋亡和炎性反应相关基因的表达。

Objective:To study the effect of long-term high-fat diet on autophagy,apoptosis and inflammation of myocardium in mice.Methods:Six-week-old male C57BL/6 mice were randomly divided into the control group and high-fat feeding group.All the mice were weighed after being fed for 24 weeks.The pericardiac and periepididymal adipose tissue were isolated and weighed to calculate the heart weight/body weight ratio.Western blot and real-time fluorescent quantitative polymerase chain reaction were used to detect changes in the mRNA and protein expression levels of autophagy,myocardial apoptosis and inflammatory response-related genes in myocardium.Results:Compared with the control group,body mass,visceral fat and heart weight were higher in the high-fat feeding group,and heart weight/body weight ratio was also higher(all P<0.05).The mRNA and protein expression of autophagy-related gene LC3Ⅱin the high-fat feeding group was lower,so did the Becn1,the core gene of autophagy(all P<0.05).The mRNA levels of apoptosis-related genes Bax and Bad were significantly higher,and the protein levels of c-caspase-3 and c-PARP,apoptosis marker proteins,were significantly higher in the high-fat feeding group(all P<0.05).The mRNA levels of inflammatory genes NLRP3,IL-1βand caspase-1 were higher in the high-fat feeding group(all P<0.05).Conclusions:Long-term high-fat diet inhibits autophagy in myocardium of mice,and increases the expression of apoptosis and inflammation related genes.