复方黄精口服液对心力衰竭大鼠心肌肌球蛋白重链变化的作用

背景阿霉素是蒽环类抗肿瘤药,对多种恶性肿瘤有抑制作用.但由于其毒性大,可引起与剂量依赖性的心脏毒性,严重者可致心力衰竭.复方黄精口服液能抗自由基损伤,有望用于心力衰竭的辅助治疗.目的探讨复方黄精口服液抗心力衰竭疗效及其作用机制.设计随机对照观察.单位福建省医科大学附属第一医院中医科、福建省中医学院及福建省中医学院.材料实验于2000-08/2001-05在福建省高血压研究所完成,选用66只雄性SD大鼠.方法采用阿霉素损伤大鼠心肌致心力衰竭为模型,66只大鼠随机分为6组,每组11只.正常组腹腔注射等体积生理盐水.阿霉素组于实验开始后第2,4天腹腔注射阿霉素1 mg/kg;第6,8天腹腔注射2 mg/kg;第10,12天腹腔注射3 mg/kg;第14,16天腹腔注射4 mg/kg,16 d累计用药量达20 mg/kg.阿霉素+复方黄精口服液2 mL(小剂量组).阿霉素+复方黄精口服液4 mL(中剂量组).阿霉素+复方黄精口服液6 mL(大剂量组).小、中、大剂量组于实验开始后分别每日用复方黄精口服液灌胃.阿霉素的剂量用法同阿霉素单用组.阿霉素+天保宁(天保宁组)天保宁450 mg/kg隔日灌服共8 d.阿霉素的剂量用法同阿霉素单用组.主要观察指标观察各组大鼠心系数,α-肌球蛋白重链,β-肌球蛋白重链的变化.结果纳入实验动物数66只,在整个实验期间阿霉素组有5只大鼠,小剂量组4只大鼠,中剂量组2只大鼠,大剂量组3只大鼠,天保宁组3只大鼠死于明显的充血性心力衰竭,进入结果分析47只.与正常组比较,阿霉素组的α-肌球蛋白重链下降20.88%(P＜0.01),β-肌球蛋白重链上升50.93%(P＜0.01),心系数升高33.83%(P＜0.01).经给药治疗后,心肌β-肌球蛋白重链向α-肌球蛋白重链转化,与阿霉素组比较,各药物治疗组α-肌球蛋白重链上调(P＜0.01),β-肌球蛋白重链下降(P＜0.01),心系数均有不同程度下降(P＜0.01或P＜0.05),以上变化以中剂量组作用最佳.结论复方黄精口服液能减轻阿霉素致心力衰竭的毒性反应,其机制与复方黄精口服液可提高心肌α-肌球蛋白重链的转化有关,且呈剂量依赖性.

Effect of compound huangjing oral liquid on myocardial myosin heavy-chain in rats with heart failure

BACKGROUND: Adriamycin is anthracycline-based drugs of anti-cancer and inhibits many malignant tumors. But due to the large toxicity, it will induce dose-dependent cardiac toxicity, resulting in heart failure in severe case. Compound huangjing oral lipid is against the injury of free radial and is expected to be applied as an assistant therapy for heart failure.OBJECTIVE: To probe into the therapeutic effect of compound huangjing oral lipid and its mechanism on heart failure.DESIGN: Randomized controlled observation was designed.SETTING: Department of Traditional Chinese Medicine , First Affiliated Hospital of Fujian University of Medical Science, Fujian College of Traditional Chinese Medicine.MATERIALS: The experiment was performed in Fujian Research Institute of Hypertension from August 2000 to May 2001, in which, 66 rats were employed and randomized into 6 groups, 11 rats in each one.METHODS: In normal group, physiological saline of equal volume was injected abdominally. In adriamycin group, adriamycin 1mg/kg was injected abdominally on the 2nd and 4th days after experiment, 2 mg/kg was injected on the 6th and 8th days, 3 mg/kg was on the 10th and 12th days and 4 mg/kg was on the 14th and 16th days. The dose was accumulated up to 20 mg/kg in 16 days. In adriamycin+compound huangjing oral liquid 2 mL (small-dose group), adriamycin +compound huangjing oral liquid 4 mL (moderate-dose group) and adriamycin+compound huangjing oral liquid 6ml (large-dose group), the oral lipid of various doses was applied for gastric perfusion everyday successively from the beginning of experiment, in which, the dose of adriamycin was same as adriamycin group. In adriamycin+tebonin group (tebonin group), tebonin 450 mg/kg was administrated once every two days, totally for 8 days, in which, the dose of adriamycin was same as adriamycin group.MAIN OUTCOME MEASURES: To observe the changes of Left ventricular weight and body weight (LVW/BW), α-MHC (myosin heavy-chain)and β-MHC.RESULTS: In the whole experiment, of 66 experimental animals, 5 rats in adriamycin group, 4 rats in small-dose group, 2 rats in moderate-dose group, 3 rats in large-dose group were died from obvious congestive heart failure, finally, 47 rats entered result analysis. Compared with normal group, in adriamycin group, α-MHC was reduced by 20.88% (P ＜ 0.01), β-MHC was increased by 50.93% (P ＜ 0.01) and LVW/BW was increased by 33.83% (P ＜ 0.01). After medication, myocardial β-MHC was transformed to α-MHC; compared with adriamycin group, α-MHC in every medical group was increased (P ＜ 0.01), β-MHC was decreased (P ＜ 0.01) and LVW/BW was decreased of different degrees (P ＜ 0.01 or P ＜ 0.05); among the above-changes, the results in moderate group were the best.CONCLUSION: Compound huangjing oral liquid alleviates toxicity of heart failure induced by adriamycin, probably due to the dose-dependence improvement of the oral liquid in myocardial α-MHC transformation.