이전|다음

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

  • role： First author第一作者
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

  • Introduction：魏小棋，男，在读博士生
WEI Xiaoqi1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

FAN Xinyi1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

JIANG Feng1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

CHAI Wangjing1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

XIAO Jinling1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

LI Fanghe1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

GAO Kuo1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

YU Xue1,  
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

WANG Wei1,  
  • role： Corresponding author通信作者
  • Affiliation：

    School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

  • Email：guoshz@bucm.edu.cn
  • Introduction：Prof. GUO Shuzhen, Ph.D., Doctoral Supervisor. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Yangguang South Street, Liangxiang Higher Education Park, Beijing 102488. E-mail: guoshz@bucm.edu.cn
GUO Shuzhen1*

추상적인

ObjectiveThis 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.MethodsThe 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.ResultsMice 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.ConclusionThis 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.

키워드

heart failure with preserved ejection fraction;traditional Chinese medicine syndrome;disease-syndrome integration;animal model;deficiency-blood stasis-toxin;mice

References

  1. [1].
    许顶立，宋霖．《中国心力衰竭诊断和治疗指南2024》解读[J]. 临床心血管病杂志，2024, 40(6): 437-439.
  2. [2].
    马丽媛，王增武，樊静，等．《中国心血管健康与疾病报告2022》要点解读[J]. 中国全科医学，2023, 26(32): 3975-3994.
  3. [3].
    REDFIELD MM, BORLAUG BA. Heart failure with preserved ejection fraction: a review[J]. JAMA, 2023, 329(10): 827-838.
  4. [4].
    MCDONAGH TA, METRA M, ADAMO M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure[J]. Eur Heart J, 2023, 44(37): 3627-3639.
  5. [5].
    HEIDENREICH PA, BOZKURT B, AGUILAR D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines[J]. Circulation, 2022, 145(18): e895-e1032.
  6. [6].
    中华中医药学会慢性心力衰竭中医诊疗指南项目组. 慢性心力衰竭中医诊疗指南(2022年)[J]. 中医杂志，2023, 64(7): 743-756.
  7. [7].
    赵慧辉，郭书文，王伟. 病证结合动物模型判定标准的建立[J]. 北京中医药大学学报，2009, 32(6): 365-367.
  8. [8].
    刘永成，石玉姣，刘思雨，等. 300例射血分数保留心力衰竭患者的中医证候分布规律[J]. 环球中医药，2024, 17(8): 27-33.
  9. [9].
    魏小棋，李帅，于江，等. 慢性心力衰竭“虚-瘀-毒”病机探析[J]. 中西医结合心脑血管病杂志，2023, 21(12): 2309-2313.
  10. [10].
    SCHIATTARELLA GG, ALTAMIRANO F, TONG D, et al. Nitrosative stress drives heart failure with preserved ejection fraction[J]. Nature, 2019, 568(7752): 351-356.
  11. [11].
    冯玄超，郭淑贞，武志黔，等．慢性心力衰竭模型大鼠气虚血瘀证相关信息的评价[J].中华中医药杂志，2014，29(5)：1563-1567.
  12. [12].
    焦文超，罗慧，唐家杨，等. 溃疡性结肠炎模型大鼠脾虚湿蕴证辨识方法研究[J]. 北京中医药大学学报，2020, 43(9): 738-745.
  13. [13].
    中国中西医结合学会活血化瘀专业委员会. 血瘀证中西医结合诊疗共识[J]. 中国中西医结合杂志，2011, 31(6): 839-844.
  14. [14].
    和振杰，时晓迟，赵英强. 基于虚、痰、瘀、毒理论浅析射血分数保留的心力衰竭炎症状态与中医药干预策略[J]. 天津中医药大学学报，2024, 43(7): 637-649.
  15. [15].
    刘悦，姚明江，梁晓，等. 瘀毒互结证动物模型的建立与评价[J]. 中国实验方剂学杂志，2023, 29(13): 72-78.
  16. [16].
    中华中医药学会，张伯礼，程海波，等. 2023年度中医药重大科学问题、工程技术难题和产业技术问题[J]. 中医杂志，2023, 64(14)：1405-1421.
  17. [17].
    郭淑贞，王伟. 中医证候形成的“三因”理论[J]. 中医杂志，2020, 61(17): 1493-1497.
  18. [18].
    FENG JY, ZHANG YH, ZHANG J. Epidemiology and burden of heart failure in Asia[J]. JACC Asia, 2024, 4(4): 249-264.
  19. [19].
    CAO Y, WANG YC, ZHOU ZQ, et al. Liver-heart cross-talk mediated by coagulation factor Ⅺ protects against heart failure[J]. Science, 2022, 377(6613): 1399-1406.
  20. [20].
    孔令越. 一氧化氮与中医“气”在脑血管病中的关系探讨[J]. 中国中医急症，2011, 20(1): 64-66.
  21. [21].
    王爱云，张婷婷，韦忠红，等. 气学理论的现代内涵研究[J]. 时珍国医国药，2020, 31(8): 1955-1957.
  22. [22].
    于泓洋，田培裕，李潇，等. 气虚血瘀证小鼠模型拓展望诊指标的应用与评价[J]. 北京中医药，2024, 43(2): 154-160.
  23. [23].
    任志鑫，王雨，张冰，等. 代谢性疾病病证结合动物模型的探讨与思考[J]. 中国实验动物学报，2022, 30(7): 897-908.
  24. [24].
    苏文全，杜雅薇，吴圣贤. 内毒致病理论的源流探析与研究思路[J]. 辽宁中医杂志，2024, 51(9): 33-36.
  25. [25].
    吴辉，杨忠奇，王陵军，等. 从毒邪致病病机学说探讨心血管疾病防治思路[J]. 新中医，2024, 56(23): 187-192.
  26. [26].
    CAMPBELL P, RUTTEN FH, LEE MM, et al. Heart failure with preserved ejection fraction: everything the clinician needs to know[J]. Lancet, 2024, 403(10431)：1083-1092.
  27. [27].
    ADEL R, IBRAHIM MFG, ELSAYED SH, et al. Oxidative stress and NF-κB/iNOS inflammatory pathway as innovative biomarkers for diagnosis of drowning and differentiating it from postmortem submersion in both fresh and saltwater in rats[J]. Int J Legal Med, 2024, 138(5): 2021-2036.
  28. [28].
    PÉREZ-CREMADES D, BUENO-BETÍ C, GARCÍA-GIMÉNEZ JL, et al. Extracellular histones trigger oxidative stress-dependent induction of the NF-κB/CAM pathway via TLR4 in endothelial cells[J]. J Physiol Biochem, 2023, 79(2): 251-260.
  29. [29].
    WANG D, YU X, GAO K, et al. Sweroside alleviates pressure overload-induced heart failure through targeting CaMKⅡδ to inhibit ROS-mediated NF-κB/NLRP3 in cardiomyocytes[J]. Redox Biol, 2024, 74: 103223.
  30. [30].
    赵鲜，麻京豫，宋朝功，等．从“痰、瘀、毒”探讨细胞焦亡与冠心病的关系[J].中医学报，2024, 39(2): 290-296.
  31. [31].
    尤越，辛高杰，刘子馨，等．急性冠脉综合征瘀毒互结证大鼠模型的建立及评价[J].中国实验方剂学杂志，2022, 28(19): 49-60.

더 읽기

The above content is generated by Large Model Translation. The translated content is for reference only. We do not assume any commercial or legal responsibilty for any consequences arising from the use of our website