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红景天苷对力达霉素诱导人二倍体成纤维细胞衰老的干预作用
引用本文:邱强,毛根祥,申佳佳,邓洪斌,李电东,王真.红景天苷对力达霉素诱导人二倍体成纤维细胞衰老的干预作用[J].中国新药杂志,2012(1):82-87.
作者姓名:邱强  毛根祥  申佳佳  邓洪斌  李电东  王真
作者单位:中国人民解放军总医院肾内科;北京协和医学院医药生物技术研究所生化室
基金项目:国家自然科学基金(81072645,81170326);国家“重大新药创制”科技重大专项(2009ZX09301-003);国家重点发展规划“973”项目(2007CB507406)
摘    要:目的:研究红景天苷对力达霉素导致DNA损伤后所诱导的细胞衰老的调节作用。方法:采用MTT法测定药物对人胚肺二倍体成纤维细胞2BS活力的影响;衰老相关的β-半乳糖苷酶染色法观察细胞衰老形态变化;流式细胞术检测细胞周期分布以及γ-H2AX蛋白表达变化;蛋白免疫印迹技术观察p53和p21蛋白表达水平变化。结果:较低浓度(低于0.1 nmol.L-1)力达霉素能够抑制2BS细胞增殖,诱导β-半乳糖苷酶染色率显著升高和G2/M期阻滞,并使DNA损伤相关的γ-H2AX蛋白以及p53和p21蛋白表达升高。红景天苷能够显著干预力达霉素诱导的上述细胞衰老样表型及相关分子信号变化。结论:红景天苷能够抑制基因毒药物所致DNA损伤及其诱导的细胞衰老。

关 键 词:红景天苷  细胞衰老  力达霉素  DNA损伤

Protection of salidroside against lidamycin-induced cellular senescence in human fetal lung fibroblasts 2BS cells
QIU Qiang,MAO Gen-xiang,SHEN Jia-jia,DENG Hong-bin,LI Dian-dong,WANG Zhen.Protection of salidroside against lidamycin-induced cellular senescence in human fetal lung fibroblasts 2BS cells[J].Chinese Journal of New Drugs,2012(1):82-87.
Authors:QIU Qiang  MAO Gen-xiang  SHEN Jia-jia  DENG Hong-bin  LI Dian-dong  WANG Zhen
Institution:1 Department of Nephrology,the General Hospital of PLA,Beijing 100853,China; 2 Department of Biochemistry,Institute of Medicinal Biotechnology,Beijing 100050,China)
Abstract:Objective: To observe the regulation action of salidroside on cellular senescence of human fetal lung fibroblasts 2BS cells induced by lidamycin(LDM)-initiated DNA damage.Methods: Cellular viability was measured with MTT method,and morphological changes were observed by senescence associated β-gal(SA-β-gal) staining.The Cell cycle distribution and γ-H2AX expression were then analyzed by FACS.p53 and p21 expressions were observed by western blotting.Results: LDM of(as low as 0.1 nmol·L-1) induced growth arrest and G2/M cell cycle arrest in 2BS cells.Other senescence markers such as SA-β-gal staining were significantly increased upon LDM exposure.Furthermore,DNA damage associated γ-H2AX and p53/p21 protein levels were enhanced by the DNA damaging agent.However,salidroside was found to significantly inhibit senescence-like phenotypes and molecular changes induced by LDM as mentioned above.Conclusion: Salidroside may protect against lidamycin-induced DNA damage and cellular senescence in 2BS cells.
Keywords:salidroside  cellular senescence  lidamycin  DNA damage
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