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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1mg/kg;第6,8天腹腔注射2mg/kg;第10,12天腹腔注射3mg/kg;第14,16天腹腔注射4mg/kg,16d累计用药量达20mg/kg。阿霉素+复方黄精口服液2mL(小剂量组)。阿霉素+复方黄精口服液4mL(中剂量组)。阿霉素+复方黄精口服液6mL(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450mg/kg隔日灌服共8d。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。
BACKGROUND: Doxorubicin is an anthracycline antitumor drug and has an inhibitory effect on various malignant tumors. However, due to its high toxicity, it can cause dose-dependent cardiotoxicity, and severe heart failure can result. Compound Huangjing oral liquid can resist free radical damage and is expected to be used for adjuvant treatment of heart failure. Objective: To explore the curative effect and mechanism of compound Huangjing oral liquid on heart failure. Design: Randomized controlled observations. Unit: Department of Traditional Chinese Medicine, First Affiliated Hospital of Fujian Medical University, Fujian Provincial College of Traditional Chinese Medicine and Fujian Provincial College of Traditional Chinese Medicine. MATERIALS: The experiment was performed at the Institute of Hypertension, Fujian Province from August 2000 to October 2001. Sixty-six male SD rats were selected. METHODS: Using doxorubicin-induced myocardial failure induced by rat heart as a model, 66 rats were randomly divided into 6 groups, 11 in each group. Normal group: intraperitoneal injection of an equal volume of saline. Adriamycin group: intraperitoneal injection of adriamycin 1 mg/kg on the 2nd and 4th days after the start of the experiment; intraperitoneal injection of 2mg/kg on the 6th and 8th days; 3mg/kg intraperitoneally on the 10th and 12th days; 14th and 16th days Intraperitoneal injection of 4mg/kg, 16d cumulative dose of 20mg/kg. Doxorubicin + Compound Huangjing Oral Liquid 2 mL (low dose group). Doxorubicin + compound Huang Jing Oral Liquid 4 mL (medium dose group). Doxorubicin + compound Huang Jing Oral Liquid 6mL (large dose group). The small, medium and large dose groups were intragastrically administered with compound Huangjing oral liquid daily after the start of the experiment. The dose of doxorubicin is the same as that of the adriamycin alone group. Adriamycin + Tianbaoning (Tianbaoning group): Tianbaoning 450mg/kg every other day for 8 days. The dose of doxorubicin is the same as that of the adriamycin alone group. MAIN OUTCOME MEASURES: The changes of heart coefficient, α-myosin heavy chain and β-myosin heavy chain were observed in each group. RESULTS: A total of 66 experimental animals were included. During the entire experimental period, there were 5 rats in the doxorubicin group, 4 rats in the low-dose group, 2 rats in the middle-dose group, 3 rats in the high-dose group, and Tianbaoning group. Three rats died of marked congestive heart failure, and 47 of the results were analyzed. Compared with the normal group, the α-myosin heavy chain in the doxorubicin group decreased by 20.88% (P<0.01), the β-myosin heavy chain increased by 50.93% (P<0.01), and the heart coefficient increased by 33.83% (P <0.01). After treatment, the cardiac β-myosin heavy chain was transformed into the α-myosin heavy chain. Compared with the doxorubicin group, α-myosin heavy chain was up-regulated in each drug treatment group (P<0.01). - Myosin heavy chain decreased (P <0.01), heart coefficient decreased to varying degrees (P <0.01 or P <0.05), the above changes to the best effect of the middle dose group. Conclusion: Compound Huangjing Oral Liquid can reduce the toxicity of adriamycin-induced heart failure. Its mechanism is related to the increase of myocardial α-myosin heavy chain turnover in a dose-dependent manner.