目的:探讨四君子汤通过调节氧化三甲胺(trimetlylamine oxide,TMAO)对心力衰竭大鼠心肌能量代谢的影响.方法:70只清洁级健康雄性SD大鼠,适应性饲养3d后,随机选取8 只作为正常组,其余大鼠采用左冠状动脉前降支结扎术制备急性心肌梗死动物模型.采用随机数字表法将造模成功的24 只大鼠分为模型组、四君子汤低剂量组(2.97 g·kg-1)、四君子汤高剂量组(11.88 g·kg-1),每组各8 只,连续灌胃给药4 周,给药体积为10 mL·kg-1,正常组和模型组大鼠给予等体积的生理盐水.采用超声心动图测定各组大鼠左心室射血分数(left ventricular ejection fraction,LVEF)、左心室短轴缩短率(left ventricu-lar fractional shortening,LVFS)、左心室舒张末期内径(left ventricular end diastolic diameter,LVDd)、左心室收缩末期内径(left ventricular end systolic diamete,LVDs)、左心室后壁舒张末期厚度(left ventricular posterior wall at end-diastole,LVPWd)、左心室后壁收缩末期厚度(left ventricular posterior wall at end-systolic,LVPWs);ELISA法检测血清N末端B型利钠肽前体(N-ter-minal pro-B type natriuretic peptide,NT-proBNP)的水平;使用比色法检测血清丙酮酸(pyruvic acid,PA)、游离脂肪酸(free fat-ty acid,FFA)水平;RT-PCR检测心肌组织CPT-1 mRNA、PDH mRNA的表达情况;采用稳定同位素稀释液相色谱-串联质谱法检测大鼠血清中TMAO的含量及心肌组织中ATP的水平;HE染色和透射电镜观察各组大鼠心肌组织结构变化.结果:与正常组比较,模型组大鼠LVDs、LVDd显著升高(P<0.01),LVEF和LVFS明显降低(P<0.01);血清PA、FFA、NT-proBNP及TMAO含量明显升高(P<0.01);大鼠心肌组织CPT-1 mRNA、PDH mRNA水平明显降低(P<0.05),ATP水平明显降低(P<0.05).与模型组比较,四君子汤各剂量组大鼠LVEF、LVFS明显升高(P<0.01);血清FFA及TMAO含量均明显降低(P<0.01);心肌组织大鼠PDH mRNA水平明显升高(P<0.05),ATP水平明显升高(P<0.01).HE染色和透射电镜发现,四君子汤可明显改善心力衰竭大鼠心肌组织结构紊乱.结论:四君子汤可调节肠道菌群代谢产物TMAO的水平,从而改善心肌线粒体能量代谢,抑制心室重塑及心力衰竭的进展.
Study on Regulation of Trimetlylamin Oxide by Four Gentlemen Decoction for Improving Myocardial Energy Metabolic Remodeling in Rats with Chronic Heart Failure
Objective:To investigate the effect of Four Gentlemen Decoction on myocardial energy metabolism substrate utilization by reg-ulating trimethylamine-N-oxide(TMAO),thereby improving mitochondrial energy metabolism in the myocardium,inhibiting myocardial remodeling,and preventing the progression of heart failure.Methods:A total of 70 healthy male SD rats were used,with 8 randomly se-lected as the normal group after 3 days of adaptive feeding.The remaining rats underwent left anterior descending coronary artery liga-tion to establish an acute myocardial infarction model.Successfully modeled rats were randomly divided into the model group,the low-dose Four Gentlemen Decoction group(2.97 g·kg-1),and the high-dose Four Gentlemen Decoction group(11.88 g·kg-1),with8 rats in each group.They were administered the corresponding doses by gavage for 4 weeks,with a dose volume of 10 mL·kg-1.The normal and model groups received an equivalent volume of normal saline.Echocardiography was used to measure left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVDd),left ventricular end-systolic diameter(LVDs),left ventricular posterior wall thickness at end-diastole(LVPWd),and left ventricular posterior wall thick-ness at end-systole(LVPWs)in each group.Serum levels of N-terminal pro-B type natriuretic peptide(NT-proBNP)were detected u-sing ELISA,while pyruvic acid(PA)and free fatty acids(FFA)levels were measured by colorimetry.RT-PCR was used to detect the expression of CPT-1 mRNA and PDH mRNA in myocardial tissue.Liquid chromatography-tandem mass spectrometry with stable isotope dilution was employed to measure TMAO levels in serum and ATP levels in myocardial tissue.HE staining and transmission electron mi-croscopy were used to observe structural changes in myocardial tissue across groups.Results:Compared with the normal group,the mod-el group showed significantly increased LVDs and LVDd(P<0.01)and significantly decreased LVEF and LVFS(P<0.01).Serum PA,FFA,NT-proBNP and TMAO levels were significantly elevated(P<0.01).CPT-1 mRNA and PDH mRNA expression in myocardi-al tissue,as well as ATP levels,were significantly decreased(P<0.05).Compared with the model group,each Four Gentlemen group had significantly higher LVEF and LVFS(P<0.01),with significantly reduced serum FFA and TMAO levels(P<0.01).PDH mRNA expression and ATP levels in myocardial tissue were significantly elevated(P<0.05).HE staining and transmission electron microsco-py revealed that Four Gentlemen Decoction significantly improved the disordered myocardial structure in rats with heart failure.Conclu-sion:Four Gentlemen Decoction can regulate the TMAO level of the gut microbiota metabolite,thereby improving myocardial mitochon-drial energy metabolism,inhibiting ventricular remodeling,and preventing the progression of heart failure.
trimetlylamine oxide(TMAO)metabolic remodelingmitochondrial energy metabolismFour Gentlemen Decoctionchronic heart failurerat
万方数据
维普
