北京中医药大学学报2025，Vol.48Issue(4)：501-515,15.DOI:10.3969/j.issn.1006-2157.2025.04.008
基于"虚-瘀-毒"病机的射血分数保留的心力衰竭病证结合动物模型的建立及评价
Establishment and evaluation of an animal model of heart failure with preserved ejection fraction integrating disease and syndrome based on the"deficiency-blood stasis-toxin"pathogenesis
摘要
Abstract
Objective This study aimed to construct an animal model of heart failure with preserved ejection fraction(HFpEF)that integrates disease and syndrome based on the"deficiency-blood stasis-toxin"pathogenesis and to evaluate it comprehensively.Methods The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester(L-NAME)and a high-fat diet.According to the random number table method,SPF-grade male C57BL/6J mice were randomly assigned to the control,L-NAME,high-fat diet,and model groups,10 in each group.Comprehensive observations and data collection on macroscopic signs(e.g.,fur condition,mental state,stool and urine,oral and nasal condition,paw and body condition,etc.)and cardiac function were performed after 10 and 16 weeks of model induction.Additionally,the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure.Furthermore,pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model.Results Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis,as well as syndrome of internal heat accumulation,including lethargy,slow response,dull paw color and oral/nasal color,exercise intolerance,abnormal platelet activation,dry feces,and dark yellow urine.The time window for these syndromes was between 10 and 16 weeks post-modeling.Cardiac function assessments revealed severe diastolic dysfunction,concentric myocardial hypertrophy,and myocardial fibrosis in the model group.Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium,enlarged cross-sectional area of cardiomyocytes,and sparse coronary microvasculature in the model group.Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group.Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome,the substantial cardiac damage was relatively limited compared to the control group.Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the"deficiency-blood stasis-toxin"pathogenesis.The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis,toxin syndrome,and syndrome of internal heat accumulation.Moreover,it can stably simulate the HFpEF state and reflect phenotypic changes in human disease.This model provides a suitable experimental platform to explore the pathogenesis of HFpEF,evaluate the effectiveness of traditional Chinese medicine(TCM)treatment regimens,and promote in-depth research on TCM syndromes of heart failure.关键词
射血分数保留的心力衰竭/证候/病证结合/动物模型/虚-瘀-毒/小鼠Key words
heart failure with preserved ejection fraction/traditional Chinese medicine syndrome/disease-syndrome integration/animal model/deficiency-blood stasis-toxin/mice分类
中医学引用本文复制引用
魏小棋,郭淑贞,范昕怡,蒋峰,柴王静,肖金陵,李芳赫,高阔,于雪,王伟..基于"虚-瘀-毒"病机的射血分数保留的心力衰竭病证结合动物模型的建立及评价[J].北京中医药大学学报,2025,48(4):501-515,15.基金项目
国家重点研发计划项目(No.2022YFC3500104) National Key R&D Program(No.2022YFC3500104) （No.2022YFC3500104）
