CAJ | 학술논문

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Mas-son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％（340/340 mg/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85/340 mg/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。
목적：건립교현유모형경우수적대제량이병신상선소（ isoproterenol ， ISO ）인기적심력쇠갈（heart failure， HF）대서모형，병대기진행평개。방법160지웅성SD대서피수궤분위4조，정상조（n＝10），85/85 mg/kg조（ n＝50），85/340 mg/kg조（ n＝50）화340/340 mg/kg조（ n＝50）。련속2천，매천량차경피하주사동원ISO，계산매조재불동시간점적사망솔。소유존활적ISO대서분별재급약2주、3주화4주후진행초성심동도검사。사혈분수（ ejection fraction， EF）＜45％적대서피정의위심력쇠갈대서，병계산EF＜45％재3개ISO조적발생솔。최후일차주사후4주，장소유대서처사，통과HE화Mas-son염색관찰염성세포침윤화심기섬유화적정도，통과면역조화관찰촉염세포인자IL-1화IL-6，IL-17적표체。결과4주후，사망솔분별위25.1％（85/85 mg/kg조），56.3％（85/340 mg/kg ），68.6％（340/340 mg/kg），3조지간차이현저。85/340 mg/kg조화340/340 mg/kg조，대서EF＜45％적백분솔화심기섬유화솔분별위100％，현저고우85/85 mg/kg조。여정상대조조상비，IL-1，IL-6화IL-17재85/340 mg/kg조중적표체현저증가。결론85/340 mg/kg ISO유도HF대서모형적효과명현우우기타량개제량。촉염세포인자재ISO유도적HF발전중발휘착중요작용。
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 .