摘要
目的应用别嘌呤醇(allopurinol,ALLO)治疗慢性心力衰竭(chronic heart failure,CHF)大鼠,探究治疗效果及机制。方法28只Wistar大鼠腹部皮下注射异丙肾上腺素(340mg/kg),间隔24h重复注射1次后随机分为CHF组及ALLO组,每组14只。8只大鼠腹部皮下注射0.9%氯化钠注射液作为对照组。自实验第3天起ALLO组每天给予ALLO灌胃(50 mg/kg),持续8周。其余两组给予0.9%氯化钠注射液灌胃。应用超声心动仪检查左心室(left ventricular,LV)结构及功能,记录LV重量与体质量的比值,行心肌HE染色及超微结构检查,测量心肌黄嘌呤氧化酶(xanthine oxidase,XO)活性和脂质过氧化产物丙二醛(malondialdehyde,MDA)含量。结果CHF组大鼠存活9只,ALLO组存活11只,两组存活率比较,差异无统计学意义(P>0.05)。与对照组比较,CHF组LV收缩末及舒张末内径增加,射血分数降低,LV重量/体质量增加,心脏XO活性及MDA含量增加(P<0.05)。与CHF组比较,ALLO组LV收缩末及舒张末内径缩小,射血分数增加,LV质量/体质量降低,心脏XO活性及MDA含量减少(P<0.05)。CHF组心肌水肿、坏死及纤维化,肌节崩解,线粒体肿胀。ALLO组上述病理改变均得以改善。结论ALLO可降低心脏XO活性,有效治疗CHF。
Objective To investigate the effect and mechanism of allopurinol(ALLO)in the treatment of rats with chronic heart failure(CHF).Methods HF model was induced in twenty-eight rats by subcutaneously abdominal injection with isoproterenol(340 mg/kg)once everyday for 2 days.They were divided into the 2 groups:CHF and ALLO group(n=14).Eight rats were injected with saline by the same way as the control group.ALLO(30 mg/kg)was given by intragastric administration at the third day for 8 weeks.Meanwhile,saline was administered in the other two groups.Left ventricular(LV)structure and function were examination,the determination of myocardial xanthine oxidase(XO)activity and malondialdehyde(MDA)content were performed.Results Nine rats were alive in CHF group and 11 in ALLO group.There was no difference in survival rate(P>0.05).Compared with the control group,LV end-systolic and end-diastolic diameter,the ratio of LV weight to body weight,myocardial XO activity and MDA content were increased,but LV ejection fraction was decreased in CHF group(P<0.05).Compared with CHF group,LV end-systolic and end-diastolic diameter,the ratio of LV weight/body weight,myocardial XO activity and MDA content were decreased,and LV ejection fraction was increased in ALLO group(P<0.05).LV myocardial edema,necrosis,collagen deposition,sarcomere disintegration and mitochondrial swelling were displayed in CHF group.ALLO improved such pathological abnormalities.Conclusion ALLO deceases myocardial XO activity and is effective to treat CHF.
作者
孙桂芳
王孝微
张静
Sun Guifang;Wang Xiaowei;Zhang Jing(Department of Internal Intensive Medicine,The First Affiliated Hospital of Harbin Medical University,Heilongjiang 150001,China)
出处
《医学研究杂志》
2019年第12期73-76,160,共5页
Journal of Medical Research
基金
黑龙江省教育厅科学技术研究项目(11521158)
