摘要
目的研究特定剂量γ射线辐射对大鼠肝细胞色素P450酶亚型CYP1A2,CYP2C9和CYP2D6蛋白表达和药物代谢活性水平的影响。方法大鼠施以总剂量6 Gy,剂量率68.34 cGy·min^(-1)的全身单次γ射线照射,照射后24 h取样。HE染色观察肝组织病理变化;Western印迹法检测肝组织CYP1A2,CYP2C9和CYP2D6蛋白表达水平;制备肝微粒体,肝微粒体0.6 g·L^(-1)与非那西丁10μmol·L^(-1)(CYP1A2底物)、双氯芬酸10μmol·L^(-1)(CYP2C9底物)和右美沙芬5μmol·L^(-1)(CYP2D6底物)孵育40 min,分别于5,10,20和40 min用液质联用法检测相应代谢产物浓度。结果与正常对照组相比,辐射组大鼠肝组织出现大量细胞变性,且局部髓窦开始轻度扩张;肝CYP1A2和CYP2C9蛋白表达水平分别升高82.8%和87.9%(P<0.05);肝CYP1A2和CYP2C9微粒体水平酶活性分别升高33.9%和33.1%(P<0.05);CYP2D6蛋白表达和药物代谢活性水平无显著差异。结论6 Gyγ射线辐射可使大鼠肝细胞变性,并诱导肝组织CYP1A2和CYP2C9蛋白表达和药物代谢活性升高。
OBJECTIVE To investigate the effect of specific dose ofγray radiation on protein expressions and drug metabolism activity levels of drug metabolizing enzymes CYP1 A2,CYP2 C9 and CYP2 D6 in the liver of rats.METHODS Rats were exposed to a total dose of 6 Gyγray(68.34 c Gy·min^(-1))and livers were taken 24 h after irradiation.HE staining was used to observe the pathological changes of liver tissue.Western blotting was applied to detect the changes of protein expression levels of CYP1 A2,CYP2 C9 and CYP2 D6 in liver tissues.Liver microsomes 0.6 g·L^(-1),phenacetin 10μmol·L^(-1)(CYP1 A2 substrate),diclofenac 10μmol·L^(-1)(CYP2 C9 substrate)and dextromethorphan 5μmol·L^(-1)(CYP2 D6 substrate)were incubated for 40 min,and the corresponding metabolite concentration was detected at 5,10,20 and 40 min by liquid chromatography-mass spectrometry method.RESULTS Compared with the control group,a large amount of cell degeneration occurred in the rat liver in the radiation group,and the local medullary sinus began to dilate slightly.The expression levels of CYP1 A2 and CYP2 C9 proteins in the rat liver in the radiation group increased by 82.8%and 87.9%,respectively(P<0.05).The activity of CYP1 A2 and CYP2 C9 microsomes in the rat liver in the radiation group increased by 33.9%and 33.1%,respectively(P<0.05).There was no significant difference in CYP2 D6 protein expression or drug metabolism activity levels.CONCLUSION 6 Gyγ-ray radiation can cause cell degeneration in rat liver tissue,and increase CYP1 A2 and CYP2 C9 protein expressions and drug metabolism activity levels to different extents.
作者
董航
张海晖
窦桂芳
孟志云
叶彤
朱晓霞
顾若兰
吴卓娜
甘慧
DONG Hang;ZHANG Hai-hui;DOU Gui-fang;MENG Zhi-yun;YE Tong;ZHU Xiao-xia;GU Ruo-lan;WU Zhuo-na;GAN Hui(Institute of Radiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2021年第4期290-296,共7页
Chinese Journal of Pharmacology and Toxicology
基金
北京市自然科学基金(7202148)。
