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基于“方证对应”理论探讨主动脉弓缩窄致心力衰竭大鼠模型的中医证型与代谢标志物 被引量:10

Exploration on Syndrome Types and Metabolic Markers of Rat Model with Heart Failure Caused by Transverse Aortic Constriction Based on Theory of Correspondence of Prescription and Syndrome
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摘要 目的:观察3种中药注射液对主动脉弓缩窄(TAC)致心力衰竭大鼠模型的疗效差异,基于“方证对应”理论探讨模型的中医证型,从代谢角度揭示方证的生物学基础。方法:对大鼠进行TAC术,造模成功将其后分为模型组、丹红注射液组(6.0 mL·kg^(-1))、参麦注射液组(6.0 mL·kg^(-1))、参附注射液组(6.0 mL·kg^(-1))和曲美他嗪组(10 mg·kg^(-1)),另设立假手术组作对照。药物干预15 d后,对各组进行超声心动图、血清氨基末端脑钠肽前体(NT-proBNP)与心肌组织病理染色检测,对比疗效以遴选有效注射液;运用比色法检测有效注射液干预后的血清糖脂代谢指标,利用超高效液相色谱-质谱法观察心肌组织代谢产物与关联代谢通路。结果:与假手术组比较,模型组左室射血分数(LVEF)和左室短轴缩短率(FS)显著下降(P<0.01),左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)和NT-proBNP水平显著上升(P<0.01)。与模型组比较,丹红注射液组LVEF和FS显著上升(P<0.01),LVIDd、LVIDs、NT-proBNP水平明显下降(P<0.05,P<0.01);参附注射液组的NT-proBNP水平明显下降(P<0.05);参麦注射液组的LVIDd明显上升(P<0.05),NT-proBNP水平显著上升(P<0.01);曲美他嗪组LVEF和FS显著上升(P<0.01),LVIDs和NT-proBNP水平明显下降(P<0.05,P<0.01)。丹红注射液组与曲美他嗪组的血清葡萄糖、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇水平明显回调(P<0.05,P<0.01);丹红注射液组的9种心肌产物回调,涉及甘氨酸、丝氨酸和苏氨酸代谢,乙醛酸和二羧酸酯代谢,甘油磷脂代谢;曲美他嗪组的10种心肌产物回调,涉及甘油磷脂代谢。结论:丹红注射液对TAC致心力衰竭模型的疗效显著且优于参附注射液与参麦注射液,推测该模型与心血瘀阻证密切关联;丹红注射液干预模型的生物学机制涉及调节糖脂代谢、氨基酸代谢、丁酸代谢紊乱。 Objective:To observe the difference in the efficacy of three kinds of traditional Chinese medicine(TCM)injections on rat model of heart failure induced by transverse aortic constriction(TAC),explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome,and reveal the biological basis of prescription-syndrome from the perspective of metabolism.Method:Rats were treated with TAC for modeling and were divided into Shenmai injection group(6.0 mL·kg^(-1)),model group,Danhong injection group(6.0 mL·kg^(-1)),Shenfu injection group(6.0 mL·kg^(-1))and trimetazidine group(10 mg·kg^(-1)),and sham operation group was set up as control.After drug intervention for 15 days,echocardiography,serum N-terminal pro-brain natriuretic peptide(NT-proBNP)and myocardial histopathological staining were performed for each group,so as to compare the efficacy to select the effective injection.Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection,and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue.Result:Compared with the sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(FS)in the model group decreased(P<0.01),while the left ventricular end-diastolic diameter(LVIDd),left ventricular internal diameter at end-systole(LVIDs)and NT-proBNP level increased(P<0.01).Compared with model group,LVEF and FS increased(P<0.01),LVIDd,LVIDs and NT-proBNP level decreased(P<0.05,P<0.01)in Danhong injection group,NT-proBNP level in Shenfu injection group decreased(P<0.05),LVIDd and NT-proBNP level increased(P<0.05,P<0.01)in Shenmai injection group,in trimetazidine group,LVEF and FS increased(P<0.01),while LVIDs and NT-proBNP level decreased(P<0.05,P<0.01).Serum glucose,low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine grou
作者 钟森杰 熊霞军 张倩 胡思远 杨梦 黄淑敏 方格 王梓仪 李琳 胡志希 ZHONG Senjie;XIONG Xiajun;ZHANG Qian;HU Siyuan;YANG Meng;HUANG Shumin;FANG Ge;WANG Ziyi;LI Lin;HU Zhixi(Institute of Traditional Chinese Medicine Diagnosis,Hunan University of Chinese Medicine,Changsha 410208,China)
出处 《中国实验方剂学杂志》 CAS CSCD 北大核心 2022年第16期130-139,共10页 Chinese Journal of Experimental Traditional Medical Formulae
基金 国家自然科学基金项目(81774208) 湖南省自然科学基金项目(2020JJ4062,2020JJ5408,2019JJ50447) 广东省重点领域研发项目(2020B1111100001) 湖南省中医药科研计划项目青年课题(2021180)。
关键词 主动脉弓缩窄(TAC) 心力衰竭(HF) 方证对应 代谢组学 生物标志物 超高效液相色谱-质谱法(UPLC-MS/MS) 氨基酸 transverse aortic constriction(TAC) heart failure(HF) correspondence of prescription and syndrome metabolomics biomarkers ultra high performance liquid chromatography-mass spectrometry(UPLC-MS/MS) amino acids
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