异丙肾上腺素和精氨酸血管加压素诱导的大鼠心肌损伤模型比较  

Comparison of rat myocardial injury models induced by isoproterenol and arginine vasopressin

作　　者：赵浩东 王秀丹 万梅绪[3,4] 李智 李德坤 乔卫[1] 鞠爱春 ZHAO Haodong;WANG Xiudan;WAN Meixu;LI Zhi;LI Dekun;QIAO Wei;JU Aichun(School of Pharmacy,Tianjin Medical University,Tianjin 300070,China;Tianjin University of Traditional Chinese Medicine,Graduate School,Tianjin 300193,China;Tianjin Tasly Pride Pharmaceutical Company Limited,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of Traditional Chinese Medicine Injections,Tianjin 300410,China)

机构地区：[1]天津医科大学药学院,天津300070 [2]天津中医药大学研究生院,天津300193 [3]天津天士力之骄药业有限公司,天津300410 [4]天津市中药注射剂新技术企业重点实验室,天津300410

出　　处：《药物评价研究》2020年第7期1239-1244,共6页Drug Evaluation Research

基　　金：天津市科技计划项目(18YFCZZC00430、17PTSYJC00090、17JCZDJC33200)。

摘　　要：目的分别建立异丙肾上腺素(ISO)和精氨酸血管加压素(AVP)诱导的大鼠心肌损伤模型,并将两种模型进行比较。方法分别建立雄性SD大鼠AVP、ISO心肌损伤模型,ISO模型组大鼠按30 mg/kg的剂量以多点sc方式给药,连续2 d,1次/d;AVP模型组大鼠尾iv精氨酸血管加压素0.05 mg/kg。超声测量心功能,监测大鼠心电图,测量大鼠血清中心钠素(ANP)、脑利钠肽(BNP)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)的水平,并对大鼠心脏进行HE染色,观察切片。结果AVP模型组大鼠心电图ST段较对照组显著上升(P<0.05),ISO模型组大鼠心电图紊乱且短期内不能恢复。超声结果显示,与对照组比较,ISO和AVP模型组大鼠的左心室舒张末期内径(LVDd)和左心室收缩末期内径(LVDs)显著增加(P<0.05),射血分数(EF)显著下降(P<0.05),E/A下降至1以下。AVP和ISO模型组大鼠ANP水平均显著高于对照组(P<0.01);ISO模型组大鼠BNP水平显著高于对照组(P<0.01)。AVP和ISO模型组大鼠CK、LDH、AST水平均显著高于对照组(P<0.05),ISO模型组大鼠CK、LDH水平均显著高于AVP模型组(P<0.05);ISO模型组大鼠SOD含量显著低于对照组(P<0.05)。HE染色结果显示,对照组心肌细胞结构清晰排列紧密,AVP模型组心肌细胞出现细胞核溶解和空泡变性,ISO模型组出现心肌组织纤维化和炎细胞浸润。结论ISO和AVP诱导的大鼠心肌损伤模型均有明显的心脏病理性改变,且前者对大鼠心肌的损伤的程度较大,初步判断可能是由于缺氧时间更长造成的。Objective To establish rat models of myocardial injury induced by isoproterenol(ISO)and arginine vasopressin(AVP),and compare the two models.Methods The AVP and ISO myocardial injury models of male SD rats were established respectively.The rats in the ISO model group were administrated in the form of multi-point sc at a dose of 30 mg/kg for 2 consecutive days,once a day;the rats in the AVP model group were administrated in the form of iv arginine vasopressin 0.05 mg/kg.The cardiac function was measured by ultrasonic cardiogram.The ECG was monitored.The levels of ANP,BNP,CK,LDH,AST and SOD in serum were determined.The hearts of the rats were HE stained and the sections of the hearts were observed.Results The ST segment of ECG in AVP group was lower than that in normal group(P<0.05),and the ECG in ISO group was disordered and could not recover in a short time.The results of UCG showed that compared with cotroll group,LVDd and LVDS in AVP group and ISO group increased(P<0.05),FS%(P<0.05)and E/A decreased.ANP level in AVP group and ISO group was higher than that in control group(P<0.01);BNP level in ISO group was also higher than that in control group(P<0.01).The levels of CK,LDH and AST in AVP and ISO model group were significantly higher than those in the control group(P<0.05),the levels of CK and LDH in ISO model group were significantly higher than those in AVP model group(P<0.05),and the content of SOD in ISO model group was significantly lower than that in the control group(P<0.05).The results of HE staining showed that the structure of myocardial cells in the normal group was clear and closely arranged,myocardial cells in the AVP group showed nucleolysis and vacuolar degeneration,and myocardial fibrosis and inflammatory cell infiltration appeared in the ISO group.Conclusion The myocardial injury models induced by ISO and AVP have obvious cardiac pathological changes,and the former caused more severe myocardial injury,which may be caused by longer hypoxia.

关 键 词：异丙肾上腺素 精氨酸血管加压素 心肌损伤 模型 心电图 心功能 缺氧 

分 类 号：R965.1[医药卫生—药理学]