槲皮素对阿霉素致小鼠心肌损伤的保护作用及其机制  

Protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism in mice

作　　者：裴天仙[1] 徐长庆[1] 李滨[2] 张卓然[1] 高秀香[1] 于靖[3] 李鸿珠[1] 杨宝峰[4] 

机构地区：[1]哈尔滨医科大学病理生理教研室,黑龙江哈尔滨150036 [2]黑龙江省中医研究院,黑龙江哈尔滨150036 [3]哈尔滨医科大学生物化学教研室,黑龙江哈尔滨150036 [4]哈尔滨医科大学药理学教研室

出　　处：《药学学报》2007年第10期1029-1033,共5页Acta Pharmaceutica Sinica

基　　金：黑龙江省科技厅国际合作课题(WC02303).

摘　　要：观察槲皮素对阿霉素致小鼠心肌损伤的保护作用并初步探讨其机制。腹腔注射阿霉素(20 mg.kg-1)复制小鼠心肌损伤模型,检测心电图、心肌超微结构,血清NO含量和iNOS活性,心肌组织LDH、SOD、MDA的水平和p53蛋白表达。并观察槲皮素(50,100及200 mg.kg-1)对上述指标的影响。阿霉素可导致小鼠心律失常和心肌超微结构损伤;使NO、iNOS、MDA和LDH的水平升高,SOD的水平降低;p53蛋白表达增强。槲皮素(50,100及200mg.kg-1)可拮抗阿霉素所致的上述变化。槲皮素对阿霉素性小鼠心肌损伤具有保护作用,其机制与增强SOD活力、降低iNOS活性、抑制p53蛋白表达等有关。This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin （ADR） at a single dose of 20 mg . kg^-l. Mice were randomly divided into 5 groups （ n = 20） ： normal control group, ADR 20 mg. kg^-1 group, quercetin （50, 100, and 200 mg. kg^-1 groups, intragastric administration, once a day, for 7 days before ADR administration ）. The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the uhrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG＇ s R wave （P 〈 0. 001 ） , increased the incidence of arrhythmia （ to 60% ） , injured myocardial uhrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 （P 〈 0. 001 ）. Compared with ADR 20 mg. kg^-1 group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression （ P 〈 0. 001, P 〈 0.01 or P 〈 0.05 ） , and markedly reduced the myocardial uhrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.

关 键 词：槲皮素 阿霉素 P53 自由基 细胞凋亡 

分 类 号：R285[医药卫生—中药学] R965[医药卫生—中医学]