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作 者:何玲[1] 孙桂波[1] 孙潇[1] 孙静[1] 孙晓波[1]
机构地区:[1]中国医学科学院药用植物研究所,北京100193
出 处:《中国药理学通报》2012年第9期1229-1234,共6页Chinese Pharmacological Bulletin
基 金:国家科技支撑计划项目(No 2008BAI51B02);国家重大新药创制科技专项(No 2009ZX09502~015);国家科技部科研院所技术开发研究专项(No 2008EG150298);国家重点基础研究发展计划(973计划)项目(No 2009CB522805)
摘 要:目的观察木犀草苷(luteoloside)对阿霉素(adriamy-cin,ADR)诱导大鼠乳鼠心肌细胞损伤的保护作用,并初步探讨其作用机制。方法采用新生SD大鼠乳鼠,差数分离提取心肌细胞,建立ADR心肌细胞损伤模型,培养48 h后随机分为正常对照组、ADR模型组、木犀草苷与ADR同时给药(12.5、6.25和3.125 mg.L-1)各剂量组及木犀草苷预孵育4 h后,与ADR同时给药(12.5、6.25、3.125 mg.L-1)各剂量组。观察木犀草苷对ADR诱导心肌细胞损伤的量效、时效关系,采用MTT法检测细胞活力、试剂盒检测乳酸脱氢酶(LDH)漏出量、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活力。结果与正常对照组相比,模型组细胞存活率降低、细胞内LDH含量降低,漏出量增加、SOD活性降低及细胞上清液中MDA含量增多。与模型组相比,木犀草苷各处理组心肌细胞存活率均明显增加(P<0.05);木犀草苷与ADR同时给药12.5、6.25 mg.L-1组(P<0.05)能明显降低LDH漏出量、增强SOD活力、降低细胞上清中MDA含量;预孵育4 h后,与ADR同时给药各剂量组均能明显降低LDH漏出量(P<0.05)、增强SOD活力、降低MDA含量(P<0.01)。结论木犀草苷对ADR所致的心肌损伤有明显保护作用;且预孵育4 h后对心肌细胞的保护作用优于未孵育组,其初步作用机制可能与抗自由基、减轻脂质过氧化作用有关。Aim To observe the protective effects of induced by adriamycin (ADR) and explore its mecha- nism of the action. Methods Primary cardiomyocytes were isolated from neonatal rats and cultured for 48 h, the cells then were randomly divided into normal control groups, ADR model glucoside ( 12. 5, 6.25, groups, ADR + luteolin-7-0- 3. 125 mg · L^-1) simuhaneously treated groups and ADR + luteolin-7-0-glucoside (12.5, 6.25, 3.125 mg· L^-1) pretreated for 4 h groups. The dose and time dependent effects of luteolin- 7-0-glucoside on myocardial injury induced by ADR were investigated. The survival rate of myocardial cells was calculated by MTF assay. The leakage of lactate dehydrogenase (LDH), the contents of malondialdehyde (MDA) and the activities of superoxide dimutase (SOD) were measured by respective kits. Results Compared with model groups, the survival rates of all luteolin-7-0-glueoside treated groups were significantly luteolin-7-0-g lucoside on neonatal rat cardiomyocytesincreased ( P 〈 0. 05 ). The content of LDH leakage was reduced, the activities of SOD were increased, and the content of MDA was reduced in ADR + luteolin-7-0- glucoside ( 12.5, 6.25 mg· L^-1 ) groups(P 〈0. 05). In the luteolin-7-0-glucoside 4 h pre-incubation groups the contents of LDH leakage were significantly reduced, activities of SOD were increased, and the contents of MDA were reduced( P 〈 0. 01 ). Conclusion Luteolin-7-0-glucoside effects on myocardial shows damage significant induced by protective ADR, and the protective effects can be improved after 4 h s' pretreatment with luteolin-7-0-glucoside. The mechanism of this may be related to the effects of anti-free radical and the inhibition of lipid peroxidation.
关 键 词:木犀草苷 心肌细胞 阿霉素 抗氧化 LDH MDA SOD
分 类 号:R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]
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