基于“以方测证”理论探讨异丙肾上腺素诱导慢性心力衰竭大鼠模型的制备及中医证型  

Preparation of a rat model of chronic heart failure induced by isoprenaline based on "inferring pattern by the formula" and its pattern types

作　　者：黄淑敏 廖晓倩 范星宇 王梓仪 胡思远[1] 胡志希[1] HUANG Shumin;LIAO Xiaoqian;FAN Xingyu;WANG Ziyi;HU Siyuan;HU Zhixi(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;The Second People's Hospital Affiliated toFujian University of Chinese Medicine,Fuzhou,Fujian 350003,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]福建中医药大学附属第二人民医院,福建福州350003

出　　处：《湖南中医药大学学报》2023年第3期368-375,共8页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金项目(82274412);湖南省自然科学基金项目(2020JJ4062,2020JJ5408);广东省重点领域研发项目(2020B1111100001);湖南省教育厅项目(21A0230,21B0361);湖南省学位与研究生教育教改项目(2020JGZX012);湖南省教育改革课题(HNJG-2021-0594);湖南省研究生培养创新基地(2019-45);湖南省学位办研究生导师团队项目(2019-111);湖南省学位办中医诊断研究生案例库建设项目。

摘　　要：目的 构建异丙肾上腺素(isoprenaline, ISO)诱导的慢性心力衰竭(chronic heart failure, CHF)大鼠模型,运用以方测证法反推其中医证型。方法 采用随机数字表法将SD大鼠分为正常组及ISO低、中、高剂量组。制备CHF大鼠模型,将成模大鼠按随机数字表法分为6组:模型组、参附组、丹红组、参麦组、黄芪组、普萘组。分别于造模结束后、给药15 d后,检测各组大鼠心脏质量指数及左心室质量指数;超声心电图检测各组大鼠心功能;ELISA法检测大鼠氨基末端脑钠肽前体(N-terminal pro brain natriuretic peptide, NT-pro BNP);HE及Masson染色方法观察大鼠心脏组织病理形态以及纤维化状态改变。结果 不同剂量ISO诱导CHF大鼠模型的制备:与正常组比较,ISO低剂量组各方面均无明显改变;ISO中、高剂量组大鼠左室射血分数(left ventricular fraction shortening, LVEF)、左室短轴缩短率(left ventricular fraction shortening, LVFS)、体质量降低(P<0.01),左心室舒张末期内径(left ventricular internal dimension diamete, LVIDD)、左心室收缩末期内径(left ventricular internal systolic dimension, LVISD)、NT-pro BNP、心脏质量指数、左心室质量指数明显升高(P<0.01),但ISO高剂量组死亡率低、炎性细胞浸润及纤维化程度更高。基于“以方测证”理论探讨ISO诱导CHF大鼠中医证型:与模型组比较,参附组LVEF、LVFS、体质量升高,LVIDD、LVISD、NT-pro BNP、心脏质量指数及左心室质量指数降低(P<0.05,或P<0.01);纤维结缔组织增生和炎性细胞浸润明显减少,胶原纤维沉积减轻,仅见少量胶原纤维。其余组各项指标均有改善,但无统计学意义(P>0.05)。结论 ISO中、高剂量均能制备CHF大鼠模型,但ISO高剂量更优。ISO诱导CHF大鼠模型可能属于心阳虚证。Objective To construct a rat model of chronic heart failure(chronic heart failure, CHF) induced by isoprenaline(ISO) and to infer its TCM pattern types based on "inferring pathogenesis by the formula". Methods SD rats were randomly divided into normal group and low-, medium-, and high-dose ISO groups. The prepared CHF rat models were divided into six groups with the random number table method: model group, Shenfu group, Danhong group, Shenmai group, Huangqi group, and propranolol group. The cardiac mass index and left ventricular mass index of each group were respectively detected after modeling, and 15 d after administration. Echocardiogram was used to detect the cardiac function in each group;ELISA was adopted to detect N-terminal pro brain natriuretic peptide(NT-pro BNP);HE and Masson staining were used to observe the histopathological morphology and fibrotic state of rat hearts. Results Preparation of ISO-induced CHF rat models with different doses: Compared with the normal ISO group, there was no significant changes in all aspects of the low-dose ISO group. In medium-and high-dose ISO dosage group,there was decrease in left ventricular fraction shortening(LVEF), left ventricular fraction shortening(LVFS), and body mass(P<0.01).However, there was significant higher left ventricular end-diastolic internal dimension diameter(LVIDD), left ventricular internal systolic dimension(LVISD), NT-pro BNP, cardiac mass index, and left ventricular mass index(P<0.01). The high-dose ISO group had lower mortality, but higher inflammatory cell infiltration and higher degree of fibrosis. TCM pattern type analysis of CHF rats induced by ISO based on "inferring pathogenesis by the formula" : Compared with model group, the LVEF, LVFS, and body mass of the Shenfu group increased, and the LVIDD, LVISD, NT-pro BNP, cardiac mass index and left ventricular mass index decreased(P<0.05, or P<0.01);fibrous connective tissue hyperplasia and inflammatory cell infiltration were significantly reduced;collagen fiber deposition decreased, and

关 键 词：以方测证 慢性心力衰竭 异丙肾上腺素 动物模型 大鼠 证型 

分 类 号：R256.2[医药卫生—中医内科学]