基于代谢组学探讨电针"内关"和"膻中"穴对慢性心力衰竭大鼠的作用机制OA

Objective To observe the effects of electroacupuncture at"Neiguan"(PC6)and"Danzhong"(CV17)on cardiac function and myocardial tissue metabolites in rats with chronic heart failure(CHF)and investigate the differences in the mechanism of action between the two acupoints.Method Twelve out of 40 specific pathogen-free(SPF)Sprague-Dawley(SD)rats were randomly selected as a control group,and the remaining rats were administered Doxorubicin hydrochloride via intraperitoneal injection to establish CHF models.The control group and the CHF-induced group each randomly contributed 4 rats for model verification.The successfully modeled rats were randomized into a model group,a Neiguan group,and a Danzhong group,with 8 rats in each group.The Neiguan group and Danzhong group received a 14-day electroacupuncture intervention,respectively.General behavioral changes,post-intervention echocardiographic parameters,and myocardial histopathological morphology were observed in the four groups;myocardial metabolites were detected using liquid chromatography-mass spectrometry(LC-MS),and metabolomic analysis was conducted using MetaboAnalyst 6.0.Result Compared with the control group,the ejection fraction(EF)and the left ventricular fractional shortening(FS)were reduced in the model group(P＜0.05),along with significantly damaged myocardial tissues under the light microscope.Compared with the model group,the EF and FS were increased in the Neiguan and Danzhong groups(P＜0.05),and histopathological damage to myocardial tissues was alleviated.Metabolomics results revealed that,compared with the control group,the model group exhibited increased levels of metabolites uracil,guanosine,and xanthine in the myocardial tissues(P＜0.05)and decreased levels of palmitoylcarnitine,adenosine diphosphate glucose,and adenylate(P＜0.05).Compared with the model group,the Neiguan group showed elevated contents of 16 metabolites in the myocardial tissues,including valine,glutamate,proline,γ-aminobutyric acid,histidine,and tyrosine(P＜0.05),and the Danzhong group demonstrated decreased contents of uridine,glutathione,fructose-6-phosphate,and creatinine(P＜0.05).Compared with the Danzhong group,the Neiguan group exhibited increased contents of adenosine diphosphoribose,taurine,valine,L-tryptophan,L-proline,uridine,glutamate,and γ-aminobutyric acid(P＜0.05),alongside decreased levels of substances like adenosine,adenine,and phenylalanine(P＜0.05).The Neiguan group primarily regulated amino acid metabolic pathways,whereas the Danzhong group mainly involved glucose metabolic pathways,among which the pyrimidine metabolic pathway was an aberrant metabolic pathway observed in the model group.Conclusion Electroacupuncture at"Neiguan"and"Danzhong"can both improve cardiac function and reduce myocardial damage in CHF rats,possibly by regulating myocardial energy metabolism through amino acid and glucose metabolic pathways.The broad regulatory effect of"Neiguan"enables holistic modulation and improvement of the pathological state in CHF,while"Danzhong"specifically targets and regulates metabolic pathways associated with myocardial injury,such as the pyrimidine metabolism.