摘要
目的探讨不同剂量的氢氯噻嗪联合制剂对心肌梗死后心衰大鼠的心功能及心肌纤维化的影响。方法通过结扎冠状动脉左前降支构建心衰大鼠模型,术后2周46只大鼠随机分为4组:假手术组(n=10)、心衰对照组(n=12)、低剂量联合组[缬沙坦20 mg+安体舒通20 mg+氢氯噻嗪12.5 mg/(kg·d),n=12]、高剂量联合组[缬沙坦20 mg+安体舒通20 mg+氢氯噻嗪25 mg/(kg·d),n=12]。药物干预8周后行超声心动图、血流动力学、血浆炎症因子水平和心肌Masson染色及胶原容积分数(CVF)的测定。结果与心衰对照组比较,低剂量联合组射血分数(EF)和左室收缩末期压(LVESP)显著提高,而左室舒张末期容积(LVEDD)及左室舒张末期压(LVEDP)降低。同时,低剂量联合组能抑制血浆白介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)的表达及减轻心肌间质纤维化和降低CVF(P<0.05),而高剂量联合组不具有类似的作用。结论氢氯噻嗪低剂量联合组具有改善心肌梗死后心衰大鼠的心功能,抑制血浆炎症因子的表达及改善心肌纤维化的作用。
Objective To explore the effects of hydrocholorothiazide combined preparation on cardiac function and myocardial fibrosis in rats with heart failure after myocardial infarction,and to explore the effects of different doses of hydrocholorothiazide.Methods Rat models of heart failure were established by ligation of the left anterior descending coronary artery.Two weeks after ligation,46 rats were randomly divided into four groups:sham-operated group(n= fO),control group(n= 12),low dose group[valsartan 20 mg/spironolactone 20 mg/hydrocholorothiazide f 2.5 mg/(kg · d),n= 12]and high dose group[valsartan 20 mg/spironolactone 20 mg/hydrocholorothiazide 25 mg/(kg · d),n= 12].Echocardiography,hemodynamic measurements,plasma proinflammatory cytokine levels and Masson's trichrome staining and collagen volume fraction were detected eight weeks after drug intervention.Results Compared with control group,the levels of ejection fraction(EF) and left ventricular end-systolic pressure(LVESP) in low dose group were significant increased,but the left ventricular end-diastolic dimension(LVEDD) and left ventricular end-diastolic pressure(LVEDP) were reduced.In addition,plasma proinflammatory cytokine levels(IL-lβ、IL-6 and TNF-α),myocardial interstitial fibrosis and collagen volume fraction in low dose group were reduced(P〈0.05).But there was no same effects observed in high dose combined group.Conclusions Low dose hydrocholorothiazide combined preparation could improve cardiac function,reduce plasma proinflammatory cytokine levels and alleviate myocardial fibrosis in rats with heart failure after myocardial infarction.
出处
《实用老年医学》
CAS
2015年第8期682-685,共4页
Practical Geriatrics
关键词
心力衰竭
利尿剂
联合用药
心功能
心肌纤维化
heart failure
diuretics
combination
cardiac function
myocardial fibrosis