慢性心阳虚大鼠模型制备改良研究  

Improvement on heart-yang deficiency rat model

作　　者：王恩慈 霍艳颖 吴实权 梁冰冰 张云茜 赵一帆 马洪海 姜代勋 霍桂桃[2] WANG Enci;HUO Yanying;WU Shiquan;LIANG Bingbing;ZHANG Yunxi;ZHAO Yifan;MA Honghai;JIANG Daixun;HUO Guitao(Beijing Key Laboratory of Traditional Chinese Veterinary Medicine,College of Animal Science and Technology,Beijing University of Agriculture,Beijing 102206,China;National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100176,China)

机构地区：[1]北京农学院动物科学技术学院/兽医学(中医药)北京市重点实验室,北京102206 [2]中国食品药品检定研究院国家药物安全评价监测中心,北京100176

出　　处：《北京农学院学报》2021年第4期64-69,共6页Journal of Beijing University of Agriculture

基　　金：北京农学院兽医学(中医药)北京市重点实验室开放课题资助。

摘　　要：【目的】对现有慢性心阳虚大鼠模型加以改良,制备更符合中(兽)医证候特点的心阳虚动物模型,为温阳方剂的作用机理研究积累资料。【方法】以盐酸多柔比星(主要成分为阿霉素)诱导法联合冰水浴寒冷刺激制备慢性心阳虚大鼠模型,耳温枪测量耳洞温度,生化分析仪检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肌酸激酶(CK)和乳酸脱氢酶(LDH)四种心肌酶活性,ELISA法测定血浆脑利钠肽(BNP)含量,多道生理信号采集处理系统监测心电图和心率变化,常规方法制作心脏切片并观察心肌病理学变化。【结果】与对照组相比,制备的慢性心阳虚模型大鼠出现精神萎靡、活动减少、身体蜷缩和扎堆等阳虚症状,且体温在造模后期的第28、35和42天明显降低(P<0.01);在造模第42天,心肌酶ALT、AST、CK、LDH活性显著升高(P<0.05/P<0.01),血浆BNP含量显著升高(P<0.05);心电图QRS间期在14、21和35天显著延长(P<0.05/P<0.01),ST段在第35、42天明显抬高(P<0.01),心率在14、21、28、35和42天明显降低(P<0.05/P<0.01);心肌组织出现空泡变性、心肌变性及轻度单个核细胞浸润。【结论】改良的盐酸多柔比星联合冰水浴寒冷刺激法可制备出具有阳虚症状和心脏损伤特征的慢性心阳虚大鼠模型,造模成功率提高。[Objective]To improve the existing rat model of heart-yang deficiency,prepareheart-yang deficiency animal model in more accordance with the characteristics of traditional Chinese(veterinary)medicine syndrome,and accumulate data for the study of mechanism of warming-yang prescriptions.[Methods]Doxorubicin hydrochloride(mainly adriamycin)combined with an ice water bath was used to make the heart-yang deficiency rat model.The temperature of the ear cavity was measured with an ear temperature gun.The activity of myocardial enzyme was detected by biochemical analyzer.Plasma brain natriuretic peptide(BNP)was measured by ELISA.The changes of electrocardiogram(ECG)and heart rate were monitored by multi-channel physiological signal acquisition and processing system.The conventional method was used to make heart sections and the histopathological change was observed.[Results]The rats in theheart-yang deficiency group had symptoms of yang-deficiency,such as mental depression,reduced activity,body curling and huddling,and the body temperature decreased on the 28th,35th and 42nd days after modeling(P<0.01).The myocardial enzymes activity of ALT,AST,CK,LDH increased(P<0.05 or P<0.01).Plasma BNP content was increased(P<0.05).The QRS interval was prolonged at 14th,21st and 35th day(P<0.05 or P<0.01),and the ST segment of ECG was increased on the 35th and 42nd day(P<0.01).Heart rate decreased at 14th,21st,28th,35th and 42nd day(P<0.05 or P<0.01).The myocardial cells showed vacuolar degeneration,myocardial degeneration and mild mononuclear cellsinfiltration.[Conclusion]Improved doxorubicin hydrochloride combined with cold stimulation in ice water bath can be used to establish a heart-yang deficiency rat model with yang-deficiency and heart injury,which has a increased success rate of modeling.

关 键 词：心阳虚 心肌酶 BNP 心电图 心肌病理学 大鼠模型 

分 类 号：R241.6[医药卫生—中医诊断学] S853.21[医药卫生—中医临床基础]