辛伐他汀诱导K562 细胞凋亡及对细胞内活性氧和Ca2+动态变化的影响

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (12): 1364-1368.

辛伐他汀诱导K562 细胞凋亡及对细胞内活性氧和Ca²⁺动态变化的影响

黄文芳, 曾娅莉¹, 刘华, 杨永长¹, 周定安

四川省医学科学院, 四川省人民医院检验科, 成都 610072, 四川;
¹重庆医科大学医学检验系, 重庆 400016

收稿日期:2006-08-30 修回日期:2006-11-01 出版日期:2006-12-26 发布日期:2020-11-06
作者简介:黄文芳, 男, 博士, 教授, 硕士生导师, 研究方向:抗肿瘤药物、微生物耐药。Tel:13981752286 E-mail:Huangwf2002@21cn.com;曾娅莉, 女, 硕士研究生, 主管检验师, 研究方向:抗肿瘤药物。Tel:13540791565 E-mail:yaya1118810@yahoo.com.cn

Changes of intracellular reactive oxygen species and Ca²⁺levels of K562 cells in process of apoptosis induced by simvastatin

HUANG Wen-fang, ZENG Ya-li¹, LIU Hua¹, YANG Yong-chang¹, ZHOU Ding-an¹

Clinical Laboratory Department, Sichuan Medical Science Academy, Sichuan Provincial People ' s Hospital, Chengdu 610072, Sichuan, China;
¹Laboratory Medicine Department, Chongqing University of Medical Sciences, Chongqing400016, China

Received:2006-08-30 Revised:2006-11-01 Online:2006-12-26 Published:2020-11-06

摘要/Abstract

摘要： 目的研究辛伐他汀诱导人红白血病细胞株K562 细胞凋亡及细胞内活性氧与Ca^{2 +}水平的变化,以探讨凋亡机制。方法 20μmol·L^-1辛伐他汀处理K562 细胞, 24 h 后光镜观察细胞形态;流式细胞术检测细胞凋亡率、活性氧和细胞内游离Ca^{2 +}水平。结果 20 μmol·L^-1辛伐他汀作用K562 细胞48 h 后出现核固缩、核碎裂和凋亡小体等形态学改变;AnnexinV-FITC/PI 检测细胞早期凋亡率, 处理组凋亡率高于对照组, 随药物作用时间延长逐渐增大, 具有时间依赖性。荧光染料2′, 7′-二氯荧光乙酰乙酸(2',7' -dichloro fluorescein diacetate, DCFH-DA) 检测K562细胞内活性氧, 不同时间处理组与对照组比较活性氧均升高, 峰值时间为24 h, 与对照组比较发生显著改变。荧光染料Fluo-3AM 检测K562 细胞内游离Ca^{2 +}浓度, 不同时间细胞内游离Ca2 +浓度均升高,峰值时间为12 h, 与对照组比较发生显著变化。结论辛伐他汀诱导K562 细胞凋亡的可能机制是通过提高细胞内活性氧及游离Ca^{2 +}水平, 从而导致细胞凋亡。

关键词: 辛伐他汀, 细胞凋亡, 细胞内钙离子, 活性氧

Abstract: AIM: To investigate the changes of reactive oxygen species (ROS) and Ca^{2 +}levels in K562 cellsinduced by simvastatin to predict the mechanism of apoptosis.METHODS: K562 cells cultivated in routinemethod were treated with 20 μmol·L^-1simvastatin.Themorphology change was observed under light microscope after 24 h.Flow cytometry assay was used to detect the apoptotic ratio, the ROS and the Ca2⁺levels.RESULTS: 24 h after K562 cells had been treated with 20μmol·L^-1simvastatin, there were some morphological changes of the cells such as karyopyknosis, nuclear fragmentation and apoptotic body emerged.AnnexinV-FITC/PI was used to detect the apoptic ratio of K562 cells, the apoptotic ratio of treated groups was markedly increased compared with the control groups in a time-dependent manner.ROS, which was detected by 2', 7' -dichloro fluorescein diacetate (DCFH-DA), was markedly increased in treated groups compared with the control groups at different time points (12, 24, 48, 72 h), and the level ROS got its peak time after 24 h.The Ca^{2 +}, which was detected by Fluo-3AM, was markedly increased in treated groups compared with the control groups at different time points, and the level ROS got its peak time after 12 h.CONCLUSION: K562 cells can be induced toapoptosis by simvastatin.The potential mechanism of apoptosis might be related to the increase of ROS and Ca²⁺level.

Key words: simvastatin, apoptosis, calcium, reactive oxygen species

中图分类号:

R965.2
R966

黄文芳, 曾娅莉, 刘华, 杨永长, 周定安. 辛伐他汀诱导K562 细胞凋亡及对细胞内活性氧和Ca²⁺动态变化的影响[J]. 中国临床药理学与治疗学, 2006, 11(12): 1364-1368.

HUANG Wen-fang, ZENG Ya-li, LIU Hua, YANG Yong-chang, ZHOU Ding-an. Changes of intracellular reactive oxygen species and Ca²⁺levels of K562 cells in process of apoptosis induced by simvastatin[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(12): 1364-1368.

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辛伐他汀诱导K562 细胞凋亡及对细胞内活性氧和Ca²⁺动态变化的影响

Changes of intracellular reactive oxygen species and Ca²⁺levels of K562 cells in process of apoptosis induced by simvastatin

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