张瑾;李秀敏;苗明三;
ZHANG Jin;LI Xiu-min;MIAO Ming-san;Henan University of Chinese Medicine;

• 1:河南中医药大学

摘要(Abstract)：

心力衰竭(heart failure,HF)发病率逐年升高,其对病人的生活质量和预期寿命都有不良影响。复制出符合临床病症特点的动物模型是开展心力衰竭相关实验研究的前提。基于心力衰竭的中医、西医临床病症特点,对现有的常用心力衰竭动物模型进行探讨,以心力衰竭中西医临床诊断标准为依据,分析已有动物模型的临床吻合度。经分析对比可知,目前已有的造模方法中,多为单因素动物模型,与临床多因素、相互作用共同导致心力衰竭的特点存在一定差距,且造模方法多以西医为指导,在造模过程中缺少中医致病因素,与临床上心力衰竭的中、西医诊断标准仍存在一定差异。从辨证分型来看,中医将心力衰竭主要分为心肺气虚证、气阴两亏证、心肾阳虚证、气虚血瘀证、阳虚水泛证、痰饮阻肺证、阴竭阳脱证,已有的动物模型多将其混为一谈,至今尚无有效且公认的造模方法,在中医药相关研究中存在较大局限性。因此,该文以心力衰竭中、西医临床病症特点为依据,分析已有动物模型,明确其优缺点及应用前景,进而提为心力衰竭相应动物模型的进一步完善、模型评价的规范化提出建议,以提高动物模型与中、西医的临床吻合度,使心力衰竭动物模型更好地服务于科研工作,促进相关机制研究、病理变化研究及药物的筛选。
The incidence of heart failure has increased year by year, with a negative impact on quality of life and life expectancy of patients. Reproduction of animal models that meet the characteristics of clinical symptoms is a prerequisite for conducting experimental studies relating to heart failure. Based on the characteristics of clinical symptoms of heart failure in traditional Chinese medicine(TCM) and Western medicine, the existing common animal models of heart failure were explored, and the clinical anastomosis of the existing animal models was analyzed based on the clinical diagnostic criteria of heart failure in TCM and Western medicine. After analysis and comparison, it can be seen that the existing modeling methods are mostly single-factor animal models, with certain gaps between the characteristics of clinical multi-factors and interactions that jointly lead to heart failure, and the modeling methods were mostly guided by Western medicine, with a lack of TCM pathogenic factors in the model process, which is different from the clinical diagnostic criteria of Chinese and Western medicine for heart failure. In terms of syndrome differentiation, heart failure is classified into heart and lung Qi deficiency syndrome, Qi and Yin deficiency syndrome, heart and kidney Yang deficiency syndrome, Qi deficiency and blood stasis syndrome, Yang deficiency and water flooding syndrome, phlegm-drinking obstructive lung syndrome, Yin and yang exhausted syndrome. The existing animal models mostly confused them, with no effective and recognized method for modeling at present. There are major limitations in studies of Chinese medicine. Therefore, based on clinical characteristics of heart failure in Chinese and Western medicine, this article analyzed the existing animal models, defined their advantages and disadvantages and application prospects, and then suggested further improving the corresponding animal models of heart failure and standardizing the model evaluation, so as to improve the clinical coincidence between animal models and Chinese and Western medicine, make heart failure animal models better serve scientific studies, and promote relevant mechanism studies, pathological change studies and drug screening.

关键词(KeyWords)： 吻合度;动物模型;临床;病症特点;心力衰竭
coincidence degree;animal model;clinical;disease characteristics;heart failure

Abstract:

Keywords:

基金项目(Foundation): 国家国际合作基地项目(2016-65);; 河南省杰出外籍科学家工作室项目(GZS2019006);; 中原学者项目(162101510003)

作者(Author): 张瑾;李秀敏;苗明三;
ZHANG Jin;LI Xiu-min;MIAO Ming-san;Henan University of Chinese Medicine;

Email:

DOI: 10.19540/j.cnki.cjcmm.20200917.602

参考文献(References)：

• [1]王建枝,钱睿哲.病理生理学[M].北京:人民卫生出版社,2018:68.
• [2]中华医学会心血管病学分会心力衰竭学组,中国医师协会心力衰竭专业委员会,中华心血管病杂志编辑委员会.中国心力衰竭诊断和治疗指南2018[J].中华心血管病杂志,2018,46(10):760.
• [3]李永渝,周平.病理生理学疾病探究[M].上海:复旦大学出版社,2014:121.
• [4]陈志强,蔡光先.中西医结合内科学[M].北京:中国中医药出版社,2012:140
• [5]何民豪.心衰病的中医文献整理[D].广州:广州中医药大学,2017.
• [6] YANCY C W,JESSUP M,BOZKURT B,et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure:a report of the American college of cardiology/American Heart Association task force on clinical practice guidelines and the heart failure society of America[J]. Circulation,2017,136(6):e137.
• [7]郑莜萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002:68.
• [8]胡元会.中医临床诊疗指南释义(心病分册)[M].北京:中国中医药出版社,2015:45.
• [9]田硕,曹利华,苗明三,等.基于临床中西医病症特点的中医药动物模型评价新方法[J].中药药理与临床,2017,33(6):165.
• [10]石峰,李文杰.心力衰竭动物实验研究进展[J].中华中医药学刊,2014,32(7):1600.
• [11]徐创业,蔺嫦燕.大动物心衰模型研究进展[J].北京生物医学工程,2013,32(5):536.
• [12]李梦婷,彭成,谢晓芳.心力衰竭小型动物模型研究进展[J].中国实验方剂学杂志,2018,24(5):213.
• [13] TIRITILLI A. DOCA-salts induce heart failure in the guinea pig[J]. Eur J Heart Fail,2001,3(5):545.
• [14] CHANG P C,LU Y Y,LEE H L,et al. Paradoxical effects of sodium-calcium exchanger inhibition on torsade de pointes and early after depolarization in a heart failure rabbit model[J].J Cardiovasc Pharmacol,2018,72(2):97.
• [15] POWERS J C,RECCHIA F. Canine model of pacing-induced heart failure[J]. Methods Mol Biol,2018,1816:309.
• [16] SPANNBAUER A,TRAXLER D,ZLABINGER K,et al. Large animal models of heart failure with reduced ejection fraction(HFr EF)[J]. Front Cardiovasc Med,2019,6:117.
• [17] ZHANG N,FENG B,MA X,et al. Dapagliflozin improves left ventricular remodeling and aorta sympathetic tone in a pig model of heart failure with preserved ejection fraction[J]. Cardiovasc Diabetol,2019,18(1):107.
• [18] SHI X,CHEN R,ZHANG Y,et al. Zebrafish heart failure models:opportunities and challenges[J]. Amino Acids,2018,50(7):787.
• [19]李晓梅,马依彤,杨毅宁,等.小鼠主动脉弓缩窄模型的建立及评价[J].中国比较医学杂志,2008,18(11):24.
• [20]邓国兴,张金兰,高玮,等.人参强心方对慢性心衰大鼠AngⅡ及其受体AT1 mRNA表达的影响[J].中国老年学杂志,2010,30(14):2031.
• [21]梁虹宇,江儒文,冯宁娜,等.超声检测加味参附颗粒对心力衰竭大鼠心脏的影响[J].内蒙古中医药,2014,33(14):52.
• [22] LEEUWENBURGH B P,STEENDIJK P,HELBING W A,et al.Indexes of diastolic RV function:load dependence and changes after chronic RV pressure overload in lambs[J]. Am J Physiol Heart Circ Physiol,2002,282(4):H1350.
• [23]张军毅.野百合碱致右心衰幼鼠Connexin43的变化及卡托普利和坎地沙坦的干预作用[D].郑州:郑州大学,2010.
• [24]李慧丽,王彬尧,张峰,等.一种慢性心力衰竭模型的建立[J].心脏杂志,2004(3):287.
• [25]李石清,宋洁,张春椿,等.参附注射液对慢性心衰大鼠心功能及心肌细胞内Ca2+浓度的影响[J].浙江中医杂志,2017,52(6):435.
• [26]项昌培,周瑞,张晶晶,等.益心舒胶囊对心力衰竭大鼠心肌细胞钙调控蛋白的影响[J].中国中药杂志,2020,45(20):4984.
• [27]张秋梅,张艳,王懿.益气活血复方对mt TFA在慢性心衰大鼠血清中表达上调的实验研究[J].中华中医药学刊,2015,33(6):1452.
• [28]张月,雷兆军,何勇.EPO对慢性心力衰竭大鼠心功能、心肌细胞凋亡及相关基因表达的影响[J].检验医学与临床,2019,16(16):2366.
• [29]游广辉.加味真武汤对阿霉素诱导心衰大鼠模型的保护作用及其机制[J].中国生化药物杂志,2015,35(11):33.
• [30]王雪梅,刘佳,付殿斌,等.参附汤萃取液成分对阿霉素致心衰大鼠血流动力学、心肌自噬及凋亡的影响[J].陕西中医学院学报,2014,37(4):75.
• [31]马晓庆,钟栩,党婵娟.参桂保心浓煎剂对心衰大鼠NT-pro BNP及caspase-3的影响[J].西部中医药,2016,29(7):8.
• [32]王洋,徐烨华,熊爱琴,等.氧化苦参碱抑制异丙肾上腺素诱导大鼠慢性心力衰竭及对ADMA代谢通路的影响[J].中国中药杂志,2014,39(3):471.
• [33]王晓燕,李七一,严士海.异丙肾上腺素诱导慢性心力衰竭大鼠模型实验研究[J].辽宁中医药大学学报,2017,19(8):31.
• [34]王学惠,卓小桢,倪雅娟,等.Neuregulin-1β对容量超负荷心衰大鼠的治疗作用[J].西安交通大学学报(医学版),2012,33(2):194.
• [35]张敏莉,肖晗,白燕,等.容量负荷和压力负荷型心脏肥大大鼠模型的建立及评价[J].中国病理生理杂志,2006,21(4):660.
• [36]韩克,吴格如,席雨涛,等.容量超负荷心力衰竭大鼠模型的制备及心脏功能的超声评价[J].中国循证心血管医学杂志,2013,5(5):507.
• [37]王萧,董浩然,麦细焕,等.主动脉瓣关闭不全法建立新西兰兔心衰模型[J].中国实验动物学报,2015,23(2):127.
• [38]许庆文,刘启德,王萧,等.血容量超负荷型兔心功能不全模型方法探讨[J].中药新药与临床药理,2002,12(3):172.
• [39]惠杰,沈振亚,焦鹏,等.快速右室起搏建立动物心力衰竭模型[J].中国心脏起搏与心电生理杂志,2004,18(6):470.
• [40] KAIMOTO S,HOSHINO A,ARIYOSHI M,et al. Activation of PPAR-αin the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure[J]. Am J Physiol Heart Circ Physiol,2017,312(2):H305.
• [41] MAKAREWICH C A,MUNIR A Z,SCHIATTARELLA G G,et al. The DWORF micropeptide enhances contractility and prevents heart failure in a mouse model of dilated cardiomyopathy[J].Elife,2018,7:e38319.
• [42]张晶,傅向华,贾辛未,等.小型猪急性心肌梗死后心力衰竭模型的构建[J].中国实验动物学报,2010,18(1):33.
• [43]李淑梅,曾凯,钟玲,等.经冠状动脉内注射自体微血栓构建大鼠急性左心衰竭模型[J].中国现代医学杂志,2007(14):1670.
• [44]马淑骅,胡剑江,王玉敏,等.黄芪注射液对两种急性心衰模型的强心作用比较[J].中国中医基础医学杂志,2011,17(4):390.
• [45]许庆文,卢传坚,欧明,等.干姜提取物对兔急性心衰模型的保护和治疗作用[J].中药新药与临床药理,2004(4):244.
• [46]张宏,彭成,展海霞,等.一种大鼠急性心力衰竭动物模型的建立方法[J].四川动物,2008,27(2):296.
• [47]杜巧辉,彭成,曹小玉,等.红参提取物对普罗帕酮所致大鼠急性心力衰竭的保护作用[J].现代临床医学,2014,40(3):175.
• [48]汪颀浩,高继海,陈海媚,等.转录组学探讨附子治疗急性心衰大鼠的作用机制[J].中国中药杂志,2019,44(1):131.
• [49]殷伟贤.全球心力衰竭现状[J].中国心血管杂志,2018,23(1):11.
• [50]马仁强,杨忠奇,寇俊萍,等.防治慢性心衰的中药新研发思路与技术要点分析[J].中国中药杂志,2020,45(11):2720.
• [51]黄明,熊可,李霄,等.心力衰竭动物模型的研究进展[J].天津中医药大学学报,2019,38(6):534.
• [52] CHEN J,STRAUSS B,LIANG L,et al. Animal model of left atrial thrombus in congestive heart failure in rats[J]. Am J Physiol Heart Circ Physiol,2019; 317(1):H63.
• [53] BOSCH L,DE HAAN J J,BASTEMEIJER M,et al. The transverse aortic constriction heart failure animal model:a systematic review and Meta-analysis[J]. Heart Fail Rev, 2020, doi:10. 1007/s10741-020-09960-w.
• [54] OKAMURA K,NAKAGAMA Y,TAKEDA N,et al. Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy[J]. J Pharmacol Sci,2019,141(1):56.
• [55]宋亚刚,李艳,崔琳琳,等.中医药病证结合动物模型的现代应用研究及思考[J].中草药,2019,50(16):3971.
• [56]柴程芝,寇俊萍,朱丹妮,等.关于病证结合动物模型研究现状的思考[J].中国中药杂志,2009,34(20):2673.
• [57] CHANG S C,REN S,RAU C D,et al. Isoproterenol-induced heart failure mouse model using osmotic pump implantation[J].Methods Mol Biol,2018,1816:207.