同分异构体补骨脂素和异补骨脂素对HepG2细胞及细胞色素P450酶的影响  

Impacts of isomers-psoralen and isopsoralen on HepG2 cells and cytochrome P450 enzymes

作　　者：刘继新[1] 高庆剑 陆铖[1,2] 王锐[1,2] 汤浩[1] 

机构地区：[1]甘肃省人民医院药剂科,兰州730000 [2]宁夏医科大学药学院,银川750000

出　　处：《中国临床药理学杂志》2014年第5期438-441,共4页The Chinese Journal of Clinical Pharmacology

基　　金：甘肃省技术研究与开发专项基金资助项目(1105TCYA024);兰州市科技计划基金资助项目(2010-1-72)

摘　　要：目的观察补骨脂素和异补骨脂素对HepG2细胞增殖、CYP基因表达及蛋白定位和蛋白表达的影响。方法用噻唑蓝(MTT)比色法、流式细胞术、实时定量PCR、免疫荧光法(IF)和Western blot检测补骨脂素和异补骨脂素对CYP1A1和CYP3A4的影响。结果在梯度浓度作用后,2种药物对HepG2细胞均有抑制作用,且存在明显的浓度依赖关系;2种药物(50μg·mL-1)均阻滞HepG2细胞周期于G2-M期,都是CYP1A1、CYP3A4 mRNA的抑制剂,但抑制效果有差别;CYP3A4蛋白表达均明显低于对照组。2种药物均抑制HepG2细胞增殖,主要是由于两者阻滞其周期于G2-M期。结论相比于补骨脂素,异补骨脂素对CYP3A4 mRNA表达和蛋白表达的抑制作用更强,而对CYP1A1mRNA的抑制强度略低。Objective To observe the effects of psoralen and isopsoralen on cell proliferation, CYP gene expression, protein localization and pro- tein expression of HepG2 cells. Methods The effects on CYP1A1 and CYF3A4 of psoralen and isopsoralen were tested by MTY colorimetry, flow cytometry determination, real time quantitative PCR technology, im- mune -fluorescence and protein immune -blot method. Results HepG2 cells were inhibited at gradient concentration by psoralen and isopsoralen. What＇s more, there was a clear dose -response relation- ship. The two drugs （50 p^g ~ mL-1） blocked HepG2 cells cycle at G2 -M phase. The two drugs were CYP1A1 and CYP3A4 mRNA inhibi- tors but with different effects. Protein expression was significantly lower than the control group. The proliferation of HepG2 cells are inhibited by the two drugs, because the cell cycle was arrested at G2 -M phase. Conclusion Compared with psoralen, isopsoralen respectively inhibited more on mRNA and protein expression of CYPSA4, but the intensity of inhibition of CYPIA1 mRNA was slightly lower.

关 键 词：补骨脂素 异补骨脂素 HEPG2细胞 细胞色素P450 

分 类 号：R282[医药卫生—中药学] R394.2[医药卫生—中医学]