不同强度运动预防高脂膳食大鼠心肌脂质沉积效果及对miR-145-5p、KLF5、PPARα表达的影响

Roles of exercise on preventing myocardial lipid deposition and miR-145-5p,KLF5,PPARαin high-fat diet rats

目的:观察12周中等强度持续运动(moderate-intensity continuous training,MICT)与高强度间歇运动(high intensity interval training,HIIT)预防高脂膳食大鼠心肌脂质沉积效果的异同,以及对miR-145-5p、KLF5、PPARα表达的影响,从而探讨其可能机制。方法:5周龄雄性SD大鼠随机分为普通膳食安静组(C组)、高脂膳食安静组(F组)、高脂膳食MICT组(M组)、高脂膳食HIIT组(H组),每组8只。12周跑台训练干预结束后,超声心动图检测大鼠心脏结构与功能;光镜和透射电镜观察大鼠心肌脂质沉积;检测大鼠血清、心肌脂质含量;RT-PCR、Western Blot和免疫荧光双标记检测大鼠心肌miR-145-5p、KLF5、PPARα的表达情况。结果:(1)与C组比较,F组大鼠心肌结构、功能受损;心肌纤维松弛,脂质沉积增多;血清及心肌脂质含量增加(P<0.05);心肌组织miR-145-5P表达升高(P<0.05),KLF5、PPARαm RNA与蛋白表达水平降低(P<0.05);KLF5、PPARα阳性细胞数降低(P<0.01)。(2)与F组比较,M、H组大鼠心肌结构、功能均改善;心肌纤维紧密,脂质沉积减少;血清及心肌脂质含量减少(P<0.01);心肌组织miR-145-5P表达降低(P<0.05),KLF5、PPARαm RNA与蛋白表达水平增加(P<0.05);KLF5、PPARα阳性细胞数增加(P<0.01)。(3)与M组比较,H组大鼠心肌脂质沉积减少;血清HDL含量增加(P<0.01),心肌TG含量降低(P<0.05);KLF5、PPARα阳性细胞数增加(P<0.01)。结论:12周MICT与HIIT均能预防高脂膳食大鼠心肌脂质沉积,大鼠心肌miR-145-5p、KLF5、PPARα表达水平的变化可能是运动影响心肌脂质代谢的机制之一,HIIT预防效果较好,可能与该信号通路的活化程度有关。

Objective:To observe the effect of moderate-intensity continuous training(MICT)and high intensity interval training(HIIT)on preventing myocardial lipid deposition in high-fat diet rats at 12 weeks,and to explore the role of miR-145-5p,KLF5,PPARαexpression.Method:Five-week-old male SD rats were randomly assigned to one of four groups:normal diet quiet(Group C),high fat diet quiet(Group F),high fat diet MICT(Group M),and high fat diet HIIT(Group H),each with eight rats.After a 12-week treadmill exercise intervention,echocardiography was used to detect the rat cardiac structure and function;light microscopy and transmission electron microscopy were used to observe myocardial lipid deposition;and serum and myocardial lipid levels were measured.The expressions of miR-145-5p,KLF5 and PPAR in rat myocardia were detected by RT-PCR,Western Blot and immunofluorescence.Result:Compared with group C,myocardial structure and function were impaired in group F;myocardial fibers were relaxed and lipid deposition was increased;serum and myocardial lipid content increased(P<0.05).The expression of miR-145-5P was increased(P<0.05),and the mRNA and protein expressions of KLF5 and PPARαwere decreased(P<0.05).The number of KLF5 and PPARαpositive cells decreased(P<0.01).Compared with group F,myocardial structure and function were improved in groups M and H;the myocardial fibers were compact and lipid deposition was reduced.Serum and myocardial lipid content decreased(P<0.01).The expression of miR-145-5P was decreased(P<0.05),and the mRNA and protein expressions of KLF5 and PPARαwere increased(P<0.05).The number of cells expressing KLF5 and PPARαincreased(P<0.01).Compared with group M,myocardial lipid deposition was decreased in group H;Serum HDL content increased(P<0.01),while myocardial TG content decreased(P<0.05).The number of cells expressing KLF5 and PPARαincreased(P<0.01).Conclusion:Both MICT and HIIT at 12 weeks can prevent myocardial lipid deposition in rats on the high fat diet,changes in the expression levels of miR-145-5p,KLF5 and PPARαin rat myocardia may be one of the mechanisms by which exercise affects myocardial lipid metabolism,the prevention effect of HIIT is better,which may be related to the activation of this signaling pathway.