槲皮素抗阿霉素诱导的培养心肌细胞的凋亡  

Effect of quercetin on rat cardiomyocyte apoptosis induced by adriamycin in vitro

作　　者：裴天仙[1] 徐长庆[1] 于靖[2] 李鸿珠[1] 郭津[1] 高秀香[1] 赵炜明[2] 杨宝峰[3] 

机构地区：[1]哈尔滨医科大学病理生理学教研室,黑龙江哈尔滨150086 [2]哈尔滨医科大学生化教研室,黑龙江哈尔滨150086 [3]哈尔滨医科大学药理学教研室

出　　处：《中国药理学通报》2008年第4期534-538,共5页Chinese Pharmacological Bulletin

基　　金：黑龙江省科技厅国际合作课题(NoWC02303)

摘　　要：目的观察槲皮素对阿霉素(adriamycin,ADR)致大鼠心肌细胞凋亡的影响。方法原代培养乳鼠心肌细胞,随机分为正常对照组、阿霉素损伤组、槲皮素对照组、阿霉素+槲皮素(低、中、高浓度)组。比色法检测培养液中乳酸脱氢酶(LDH)的活性,MTT法测定心肌细胞存活率,电镜观察细胞超微结构,免疫细胞化学法检测Bcl-2和Bax蛋白的表达,用RT-PCR和Western blot检测caspase-3 mRNA和蛋白的表达。结果与正常对照组相比,槲皮素对照组各指标无明显改变,阿霉素组LDH活性增强,细胞存活率降低,Bcl-2表达减少,Bax表达增加,心肌细胞超微结构损伤明显,caspase-3 mRNA和蛋白的表达均升高;高中低剂量槲皮素均可减轻阿霉素所致的损伤。结论槲皮素对ADR致培养心肌细胞凋亡具有保护作用,其机制与调节细胞内凋亡相关蛋白caspase-3、Bcl-2和Bax的表达有关。Aim To observe the protective effect of quercetin on rat cardiomyocyte apoptosis induced by adriamycin and explore its possible mechanism. Methods Cultured neonatal rat cardiomyocytes were randomly divided into six groups：normal control group, adriamycin group, quercetin control group, adriamycin ＋ quercetin（25,50,100μmol ·L^-1） groups. The activity of LDH was detected by chromatometry, the cardiomyocyte viability was measured by MTT, the ultrastructure of cardiomyocyte was observed by electron microscope, the expression of protein Bcl-2 and Bax was analyzed by immunocytochemical, and the mRNA and protein of caspase-3 were detected by RT-PCR and Western blot respectively. Results Compared with the control group, the activity of LDH was increased but the viability of cardiomyocyte was decreased; the expression of Bax and caspase-3 was up-regulated while Bcl-2 was down-regulated in ADR group. Compared with ADR group, the above changes were lightened in adriamycin ＋ quercetin groups. But the quercetin control group, in which cultured myocardial cells only exposed to quercetin without ADR, had no obvious changes. Conclusions Quercetin significantly inhibits the apoptosis induced by ADR in the cultured myocardial cells. Its mechanism is involved in the apoptosis-related pathways, including caspase-3, Bax and Bcl-2.

关 键 词：槲皮素 阿霉素 心肌细胞 凋亡 CASPASE-3 

分 类 号：R-332[医药卫生] R282.71