北京中医药大学学报2025，Vol.48Issue(7)：919-932,14.DOI:10.3969/j.issn.1006-2157.2025.07.006
基于"虚-瘀-毒"病机的冠心病急性心肌梗死病证结合动物模型构建与评价研究
Research on the construction and evaluation of an animal model of coronary heart disease and acute myocardial infarction based on the pathogenesis of"deficiency,stagnation,and toxicity"
摘要
Abstract
Objective To establish and evaluate a mouse model of acute myocardial infarction(AMI)with coronary heart disease(CHD)that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.Methods Forty-eight ICR mice were randomly divided into four groups using a random number table:sham-operated,normal diet,high-choline,and trimethylamine N-oxide(TMAO).From weeks 1 to 8,each group received corresponding dietary and water interventions.From the 9th week,the normal diet,high-choline,and TMAO groups underwent coronary artery ligation(left anterior descending artery,LAD).In contrast,the sham-operated group only had suture placement without ligation,maintaining the same dietary and water interventions.Data on general signs,body weight,food and water intake,urine and feces,auricle and paw conditions,and behavioral patterns were collected and compared macroscopically and microscopically to determine the syndrome type of the high-choline-induced AMI mouse model and observe changes in the"deficiency-stagnation-toxicity"syndrome indicators.After 12 weeks,echocardiography,hematoxylin-eosin(HE)staining,and Masson′s trichrome staining were used to assess cardiac function,myocardial tissue cellular morphology changes,and myocardial fibrosis levels,respectively.The stability and reliability of the model were evaluated by observing the fluorescence intensity of inflammatory cytokines in the myocardial tissues of each group using immunofluorescence.Results Mice in all groups post-AMI surgery exhibited significant weight loss,dull fur,lethargy,and reduced activity.Mice in the high-choline and TMAO groups showed more sluggish responses to stimuli.The high-choline and TMAO groups displayed increased food intake but slow weight gain from weeks 1 to 4,developing into a trend of"increased food and water intake with weight loss"from 5 to 8 weeks,accompanied by yellowish urine and dry stools(P<0.01).Postoperatively(9-12 weeks),body weight significantly decreased,with the most prominent weight loss observed in the high-choline group.The high-choline and TMAO groups exhibited abnormal RGB values in auricles and paws(P<0.01),and behavioral tests showed a significant decline in open-field activity(P<0.01).Cardiac function and pathological examinations revealed that,compared with the sham-operated and normal diet groups,mice in the high-choline and TMAO groups had increased left ventricular end-diastolic and end-systolic volumes(P<0.01),decreased left ventricular ejection fraction and fractional shortening(P<0.01),and elevated heart indices(P<0.05).HE staining of myocardial tissues indicated more pyknotic nuclei and inflammatory cell infiltration in the high-choline and TMAO groups.Masson′s trichrome staining showed extensive blue-stained collagen fiber distribution in the infarct border zones of the high-choline and TMAO groups,with aggravated fibrosis(P<0.05).Immunofluorescence revealed elevated interleukin-1 beta and tumor necrosis factor-alpha levels in the high-choline and TMAO groups compared with the sham-operated and normal diet groups(P<0.01).Conclusion A high-choline diet combined with LAD ligation successfully established an animal model of AMI with CHD that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.This model not only embodies the traditional Chinese medicine theory′s understanding of the pathogenic features of"deficiency-stagnation-toxicity",but also serves as a reference for assessing the interventional effects of Chinese herbal compound prescriptions and facilitating research on syndrome patterns in traditional Chinese medicine.关键词
冠心病/急性心肌梗死/虚-瘀-毒/证候/病证结合/动物模型/小鼠Key words
coronary heart disease/acute myocardial infarction/deficiency-stasis-toxicity/syndrome/disease-syndrome combination/animal model/mice分类
医药卫生引用本文复制引用
钱向毅,郭淑贞,范昕怡,崔伶雯,何奥龙,高阔,李芳赫,于雪,王伟..基于"虚-瘀-毒"病机的冠心病急性心肌梗死病证结合动物模型构建与评价研究[J].北京中医药大学学报,2025,48(7):919-932,14.基金项目
国家重点研发计划项目(No.2022YFC3500104) National Key R&D Program of China(No.2022YFC3500104) （No.2022YFC3500104）
