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作 者:仇炜[1] 林俊[1] 张磊[1] 朱一辰[1] 张健[1] 孙雯[1] 马麟麟[1] 田野[1]
机构地区:[1]首都医科大学附属北京友谊医院泌尿外科,北京市100050
出 处:《中国分子心脏病学杂志》2017年第1期1992-1995,共4页Molecular Cardiology of China
基 金:国家自然科学基金面上项目(81372737)
摘 要:目的顺铂是膀胱癌化疗的一线药物,但部分患者在使用后可发生心脏毒性。该作用多由顺铂引起的细胞凋亡、氧化应激、内质网应激等引起。山奈酚是一种常见的黄酮类化合物,该药具有抗氧化、抗心脏缺血-再灌注损伤的作用。本研究主要探讨山奈酚对顺铂引起心脏毒性的保护作用。方法与结果采用顺铂联合山奈酚处理H9c2心肌细胞系及原代乳大鼠心肌细胞,发现山奈酚可显著抑制顺铂引起的细胞活力下降。TUNEL结果显示,顺铂联合山奈酚处理组TUNEL阳性细胞比例较单纯顺铂处理组显著降低。山奈酚还可显著抑制顺铂诱导的心肌细胞Caspase3剪切体表达水平。然而,在膀胱癌T24细胞中,山奈酚可显著增强顺铂对该细胞的杀伤作用。结论山奈酚对顺铂诱导的心肌细胞凋亡有抑制作用。因此,山奈酚很可能是一种新的膀胱癌顺铂治疗辅助药物。Objective Cisplatin is a first-line drug for bladder cancer, however, it has potential cardiotoxicity for some patients. These side effects mostly dependent on apoptosis, oxidative stress and endoplasmic reticulum stress induces by cisplatin. Kaempferol (Kae), a common flavonoid, was found to have anti-oxidative stress and anti-ischemia/reperfusion injury effects. Therefore, this study aimed to investigate whether Kae could alleviate cisplatin-induced cardiotoxicity. Methods and Results H9c2 cells and neonatal rat cardiomyocytes (NRCM) were treated with cisplatin with or without Kae. We found that Kae could significantly antagonize cisplatin-related cytotoxicity. Kae reduced the number of TUNEL positive ceils and the cleavage of Caspase3 induced by cisplatin, which indicated that Kae may protect cardiomycytes through inhibiting cisplatin-induced apoptosis. However, Kae enhanced the anti-tumorous effects of cisplatin on human bladder cancer T24 cells. Conclusion Kae inhibits cisplatin-induced cardiotoxicity. Therefore, Kae may be used in the cisplatin therapy of bladder cancer..
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