【作者】 徐璇； 丁攀婷； 周竞颖； 何灏龙； 刘密； 钟欢； 常小荣；

【Author】 XU Xuan;DING Pan-ting;ZHOU Jing-ying;HE Hao-long;ZHONG Huan;LIU Mi;Chang Xiao-rong;College of Acupuncture-Moxibustion & Tuina and Rehabilitation,Hunan University of Chinese Medicine;College of Rehabilitation and Health Care,Hunan College of Traditional Chinese Medicine;

【机构】 湖南中医药大学针灸推拿与康复学院； 湖南中医药高等专科学校康复保健学院；

【摘要】 目的:观察电针"内关"和电针"膻中"对慢性心力衰竭大鼠心功能及心肌组织代谢物的影响,分析两穴的作用机制差异。方法:SPF级SD大鼠40只,随机挑选空白组12只,其余28只大鼠以腹腔注射盐酸多柔比星法制备CHF大鼠模型。将造模成功的大鼠随机分为模型组、电针"内关"组和电针"膻中"组,每组8只。"内关"组和"膻中"组予以电针干预20 min/d,疏密波,频率2/100 Hz,强度为1 m A,持续14 d。实验期间记录各组大鼠一般行为学变化;干预结束后超声心动图检测各组大鼠心功能;HE染色观察心肌组织病理形态学变化;液相色谱-质谱联用(LC-MS)检测心肌代谢物,利用Metabo Analyst 6.0进行代谢组学分析。结果:造模后,与空白组比,模型组大鼠射血分数(EF)、左室内径缩短率(FS)显著下降(P<0.05),光镜下心肌组织明显损伤;电针治疗后,与模型组比较,电针"内关"组和电针"膻中"组EF、FS均升高(P<0.05),心肌组织病理损伤减轻。代谢组学结果显示,与空白组相比,模型组大鼠心肌组织中代谢物尿嘧啶、鸟苷、黄嘌呤、吲哚乙醛、4-乙基苯甲酸含量上升(P<0.01),棕榈酰肉碱、腺苷二磷酸葡萄糖、腺苷酸、十六烷二酸含量下降(P<0.01);与模型组相比,电针"内关"组心肌组织中5-氨基戊酸盐、缬氨酸、2-氨基异丁酸盐、3-氨基异丁酸、二甲基甘氨酸、γ-氨基丁酸等16种代谢物含量上升(P<0.01),电针"膻中"组中尿苷、谷胱甘肽、6-磷酸果糖、肌酐、对乙基苯甲酸含量下降(P<0.01);与膻中组相比,"内关"组腺苷二磷酸核糖酸、S-腺苷高半胱氨酸、牛磺酸、缬氨酸、5-氨基戊酸、3-氨基水杨酸、L-色氨酸、L-脯氨酸、尿苷、谷氨酸、L-α-氨基丁酸、γ-氨基丁酸等含量上升(P<0.01),腺苷、腺嘌呤、苯丙氨酸、L-苯丙氨酸、异柠檬酸、D-苏糖异柠檬酸下降(P<0.01)。电针"内关"组和电针膻中的差异性代谢物所涉及的代谢通路主要为丙氨酸、天冬氨酸和谷氨酸代谢、精氨酸生物合成、丁酸酯代谢、精氨酸和脯氨酸代谢、嘌呤代谢、组氨酸代谢、柠檬酸循环(TCA循环)、牛磺酸和次牛磺酸代谢及苯丙氨酸代谢等通路。结论:电针内关和电针膻中均可改善CHF大鼠的心功能,减轻心肌损伤,其机制可能是通过改善心肌氨基酸、葡萄糖等相关通路调节心机能量代谢,而电针内关穴调节范围更加广泛,而膻中组更具有靶向性。更多还原

【Abstract】 Objective To observe the effects of electroacupuncture at " Neiguan"(PC6) and " Danzhong"(RN17) on cardiac function and myocardial tissue metabolites in rats with chronic heart failure(CHF),and to analyze the differences in their mechanisms of action.Methods 40 SPF-grade SD rats were randomly selected,with 12in the normal group(NG) and the remaining 28 rats used to establish a CHF model by intraperitoneal injection of doxorubicin hydrochloride.The successfully modeled rats were randomly divided into the model group,the electroacupuncture PC6 group,and the electroacupuncture RN12 group(n=8 rats/group).The electroacupuncture PC6 group and the electroacupuncture RN12 group received electroacupuncture intervention for 20 minutes per day,using sparse-dense waves with a frequency of 2/100 Hz and an intensity of 1 m A for 14 consecutive days.During the experimental period,general behavioral changes in rats of each group were recorded;after the intervention,cardiac function was assessed using echocardiography;histopathological changes in myocardial tissue were observed with HE staining;myocardial metabolites were detected using liquid chromatography-mass spectrometry(LC-MS),and metabolomic analysis was conducted using MetaboAnalyst 6.0.Results Compared with the NG group,the ejection fraction(EF) and fractional shortening(FS) of the model group rats significantly decreased(P<0.05),and myocardial tissue was significantly damaged under light microscopy;after electroacupuncture treatment,compared with the model group,both the electroacupuncture Neiguan group and the electroacupuncture Danzhong group showed increased EF and FS(P<0.05),and histopathological damage to myocardial tissue was reduced.Metabolomic results showed that,compared with the normal group,the content of metabolites such as uracil,guanosine,xanthine,indole acetaldehyde,and 4-ethyl benzoic acid in the myocardial tissue of the model group rats increased,while the content of palmitoylcarnitine,adenosine diphosphate glucose,adenylate,and hexadecanedioic acid decreased(P<0.01);compared with the model group,the content of 16 metabolites in the myocardial tissue of the electroacupuncture Neiguan group increased,including 5-aminovalerate,valine,2-aminoisobutyrate,3-aminoisobutyrate,dimethylglycine,and γ-aminobutyric acid(P<0.01),and in the electroacupuncture Danzhong group,the content of uridine,glutathione,fructose-6-phosphate,creatine,and p-ethyl benzoic acid decreased(P<0.01);compared with the Danzhong group,the electroacupuncture Neiguan group showed increased content of adenosine diphosphate ribose,S-adenosylhomocysteine,taurine,valine,5-aminovalerate,3-aminosalicylic acid,L-tryptophan,L-proline,uridine,glutamate,L-α-aminobutyrate,and γ-aminobutyric acid,while the content of adenosine,adenine,phenylalanine,L-phenylalanine,isocitrate,and D-sorbitol isocitrate decreased(P<0.01).The differential metabolites of the electroacupuncture Neiguan and Danzhong groups were mainly involved in metabolic pathways such as alanine,aspartate,and glutamate metabolism,arginine biosynthesis,butyrate metabolism,arginine and proline metabolism,purine metabolism,histidine metabolism,citrate cycle(TCA cycle),taurine and hypotaurine metabolism,and phenylalanine metabolism.Conclusion Both electroacupuncture at Neiguan and Danzhong can improve cardiac function and reduce myocardial damage in CHF rats,possibly by regulating myocardial energy metabolism through pathways related to amino acids and glucose.The electroacupuncture at Neiguan has a broader regulatory range,while the Danzhong group is more targeted.更多还原