不同剂量别嘌呤醇对阿霉素诱导慢性心力衰竭大鼠心功能的影响

The effects of allopurinol in different dose on the heart function of chronic heart failure rats induced by adrimydn.

目的研究不同剂量别嘌呤醇对阿霉素诱导慢性心力衰竭大鼠心功能的影响，探讨别嘌呤醇在改善心力衰竭大鼠血管内皮功能及心室重构方面是否具有剂量依赖性，从而为临床治疗心力衰竭提供理论依据和新思路。方法40只Sprague-Dawley（SD）雄性大鼠随机分为4组：正常对照组（A组）、模型对照组（B组）、别嘌呤醇低剂量组（C组）、别嘌呤醇高剂量组（D组）。经腹腔注射阿霉素建立心力衰竭模型，模型成功后A组和B组经口灌注安慰剂，C组经口灌注别嘌呤醇20mg／（kg·d），D组经口灌注别嘌呤醇40mg／（kg·d）。于灌药4周后处死大鼠测心功能、血清生化指标、心脏重量指数及电镜下观察心肌病理学变化。结果与正常对照组比较，模型对照组及各治疗组大鼠的体重均明显减轻[A组（300．10±9．85）g、B组（200．67±9．91）g、C组（233．14±9．42）g、D组（248．25±13．34）g，P〈0．05]，全心重量亦明显减轻[A组（828．30±50．97）mg、B组（681．50±16．97）mg、C组（743．00±17．20）mg、D组（784．88±36．83）mg，P〈0．05]，而全心重量指数增加[A组（2．76±0．15）mg/g、B组（3．41±0．17）mg／g、C组（3．26±0．76）mg／g、D组（3．11±0．65）mg／g，P〈0．05]；药物组血流动力学显示心肌收缩力加强；血清生化显示一氧化氮（NO）、超氧化物歧化酶（SOD）较模型对照组明显升高[B组NO（41．55±6．28）μmol／L、C组（52．47±5．59）μLmol／L、D组（61．04±4．26）μmol／L；B组SOD（63．83±6．40）U／ml、C组（76．29±7．99）U／ml、D组（100．13±7．43）U／ml，P均〈0．05]，丙二醛（MDA）明显降低[B组MDA（9．70±1．08）μmol／L、C组（6．64±0．34）μmol／L、D组（5．72±0．71）μmol／L，P〈0．05]；D组NO、SOD较C组明显升高（P〈0．05），MDA明显降低（P〈0．05）；病理学显示心肌细胞病变明显减轻。结论别嘌呤醇对改善血管内皮功能具有明显的剂量依赖性，较大剂量的别嘌呤醇能显著降低MDA，升高NO、SOD，从而更好地改善心力衰竭大鼠的心功能。

Objective To study the effects of allopurinol in different dose on the cardiac function of chronic heart failure rats induced by adrimycin. To explore dose-dependency of allopurinol in improving blood vessel endothelium function and cardiac ventricle remodeling of the rats heart, as to supply evidence and new sight in clinical treatment of congestive heart failure. Methods 40 Sprague-Dawley male rats were randomly divided into four groups： normal control group （group A）.model control group （group B ）.low-dose allopurinol group （group C ）. high-dose allopurinol group （ group D）. The heart failure model was made by administering adriamycin to rats. After the model succeeded, group A and B were treated with placebo, group C and D were treated with allopurinol 20 mg/（kg· d） and 40 mg/（kg · d）. After four weeks, the cardiac functions, blood biochemistry indexes, heart weight indexes and myocardial pathological changes were detected. Results Compared with the normal control group, the weight and heart weight of rats in model control group and allopurinol groups were obviously lessen （group A = （300. 10 ± 9.85） g,group B = （200.67 ±9.91 ）g, group C = （233.14 ± 9.42） g, group D = （248.25 ± 13.34） g; group A = （828.30 ±50.97） mg, group B = （681.50 ± 16.97） mg, group C = （743.00 ± 17.20） mg, group D = （784.88 ± 36.83 ）mg, P 〈 0. 05 ）. Heart weight indexes were all incerased （group A = （2.76 ±0. 15）mg/g, group B = （3.41 ± 0.17 ） mg/g, group C = （ 3.26±0. 76 ） mg/g, group D = （ 3.11 ± 0.65 ） mg/g, P 〈 0. 05 ）. The hemodynamics result showed that myocardial contractile force were enhanced in drug groups. The level of NO, SOD were increased in the allopurinol groups compared with the model control group （group B：NO = （41.55 ±6.28）μmol/L,group C：NO = （ 52.47 ± 5.59 ） μmol/L, group D ： NO = （ 61.04 ±4.26 ） μmol/L; group B ： SOD = （63.83 ± 6.40） U/ml, group C ： SOD = （76.29±7.99）U/ml,group D：SOD = （100.13 ±7.43）U/ml,P 〈 0.05） and MDA levels were obviously decreased（ group B ： MDA = （ 9.70 _± 1.08 ）μmol/L, group C ： MDA = （ 6.64 _± 0.34 ） μmol/L, group D ： MDA = （ 5.72 ±0. 71 ） μmol/L, P 〈 0.05 ）. The level of NO, SOD were obviously increased in the allopurinol of high-dose group compared with low-dose allopurinol group （P 〈 0.05 ）. MDA levels were obviously decreased （P 〈 0.05 ）. The myocardial pathological changes were relieved obviously in the allopurinol groups. Conehtsion Allopurinol improves blood vessel endothelium function dose-dependently. High-dose allopurinol ohviously decreases MDA, improve NO, SOD, thereby can improve the cardiac function of heart failure.