ISO诱导心力衰竭大鼠模型的建立及评价  

Establishment and evaluation of ISO induced heart failure rat model

作　　者：张依娜[1] 冯微微[1] 陈桂英[1] 马牧欣[1] 

机构地区：[1]哈尔滨医科大学附属第一医院心内科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2013年第5期410-413,共4页Journal of Harbin Medical University

摘　　要：目的建立较现有模型更优秀的大剂量异丙肾上腺素(isoproterenol,ISO)引起的心力衰竭(heart failure,HF)大鼠模型,并对其进行评价。方法 160只雄性SD大鼠被随机分为4组,正常组(n=10),85/85 mg/kg组(n=50),85/340 mg/kg组(n=50)和340/340 mg/kg组(n=50)。连续2天,每天两次经皮下注射同源ISO,计算每组在不同时间点的死亡率。所有存活的ISO大鼠分别在给药2周、3周和4周后进行超声心动图检查。射血分数(ejection fraction,EF)<45%的大鼠被定义为心力衰竭大鼠,并计算EF<45%在3个ISO组的发生率。最后一次注射后4周,将所有大鼠处死,通过HE和Masson染色观察炎性细胞浸润和心肌纤维化的程度,通过免疫组化观察促炎细胞因子IL-1和IL-6,IL-17的表达。结果 4周后,死亡率分别为25.1%(85/85 mg/kg组),56.3%(85/340 mg/kg),68.6%(340/340mg/kg),3组之间差异显著。85/340 mg/kg组和340/340 mg/kg组,大鼠EF<45%的百分率和心肌纤维化率分别为100%,显著高于85/85 mg/kg组。与正常对照组相比,IL-1,IL-6和IL-17在85/340 mg/kg组中的表达显著增加。结论 85/340mg/kg ISO诱导HF大鼠模型的效果明显优于其他两个剂量。促炎细胞因子在ISO诱导的HF发展中发挥着重要作用。Objective To establish a more excellent isoproterenol （ISO） induced heart failure （HF） rat model and to evaluate it. Methods One hundred sixty SD rats were randomly divid- ed into 4 groups, normal group （ n = 10）, 85/85 mg/kg group （ n = 50）, 85/340 mg/kg group （n = 50） and 340/340 mg/kg group （ n = 50）. The latter three groups of rats received subcu- taneous injection of homologous ISO for 2 successive days, twice a day. Mortality of each group at different time points was calculated. Echocardiography was performed on survival rats 2 week, 3 week, and 4 weeks after drug administration. Ejection fraction（EF） 〈45% rats were defined as heart failure, and incidence of EF 〈 45 % in the 3 ISO group was calculated. All rats were sacrificed 4 weeks after the last injection. HE and Masson staining were performed to evaluate inflammatory cell infiltration and myocardial fibrosis, immunohistochemistry was per- formed to evaluate expressions of IL-1, IL-6 and IL-17. Results After 4 weeks, mortality rates in three ISO-injected groups reached 25.1% （85/85 mg/kg group）, 56.3% （85/340 mg/kg） , and 68.6% （340/340 mg/kg）. Difference between the 3 groups was significant.In addition, EF 〈45% rate and myocardial fibrosis rate of 85/340 mg/kg group and 340/340 mg/kg group were 100% , significantly higher than those of the 85/85 mg/kg group. Compared with normal control group, the expression of pro-inflammatory factor （ IL-1, IL-6, IL-17） were significantly increased. Conclusion 85/340 mg/kg is an optimum dose for ISO induced heart failure rat model. Pro-inflammatory cytokines contributes to ISO induced HF.

关 键 词：ISO诱导HF大鼠模型 心肌纤维化 促炎细胞因子 

分 类 号：R542.23[医药卫生—心血管疾病]