虚寒状态下药物代谢酶CYP3A和转运蛋白P-gp变化的体内外实验研究  

Changes of drug metabolic enzyme CYP3A and transportprotein P-gp in vitro and in vivo in deficiency cold state

作　　者：薛春苗[1] 张冰[2] 李连珍[3] 林志健[2] 

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学中药学院 [3]河南农业大学农学院

出　　处：《北京中医药大学学报》2014年第9期602-605,I0001,共5页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家重点基础研究发展计划(973计划)资助课题(No.2007CB512605);北京中医药大学科研创新团队项目(No.2011-CXTD-14);北京中医药大学自主创新课题(No.2013-JYBZZ-JS-063)

摘　　要：目的通过体内外实验探讨虚寒状态下药物代谢酶CYP3A和转运蛋白P-gp变化。方法连续14 d每天肌注氢化可的松粉针剂(20 mg/kg)制造虚寒大鼠模型,观察正常、虚寒大鼠肝、小肠CYP3A活性和小肠P-gp蛋白水平;选用L02细胞和Caco-2细胞作为细胞模型,分别用正常和虚寒状态大鼠血清对其进行干预,分别观察L02细胞中CYP3A活性和Caco-2细胞中P-gp蛋白水平。结果虚寒模型大鼠肝和小肠微粒体CYP3A活性显著降低(P<0.05),小肠P-gp蛋白表达显著降低(P<0.05)。虚寒状态L02细胞中CYP3A活性明显降低(P<0.05),但虚寒状态Caco-2细胞中P-gp蛋白水平没有显著变化。结论体内、外实验共同验证了虚寒状态下CYP3A活性处于低下状态,至于Caco-2细胞中P-gp没变化,可能与Caco-2细胞株本身为癌细胞,P-gp高表达有关。Objective To discuss the changes of drug metabolic enzyme CYP3A and transportprotein P-gp in deficiency cold state through in vitro and in vivo tests.Methods The rat model of deficiency cold was established by injection of hydrocortisone （20 mg/kg） for 14 d.The activity of CYP3A and P-gp level in liver and small intestine were observed in normal and deficiency cold rats.L02 cells and Caco-2 cells were chosen as cell model and intervened with serum of normal and deficiency cold rats for observing the activity of CYP3A in L02 cells and P-gp level in Caco-2 cells.Results The activity of CYP3A decreased significantly in liver and small intestine （P ＜ 0.05）,and P-gp level decreased significantly in small intestine （P ＜0.05） in deficiency cold rats.The activity of CYP3A decreased significandy in L02 cells （P ＜ 0.05）,but P-gp level had no changes in Caco-2 cells in deficiency cold rats.Conclusion The tests in vitro and in vivo have verified that the activity of CYP3A is lower in deficiency cold state.Non-change of P-gp level in Caco-2 cells may be related to that Caco-2 cells are cancer cells and P-gp expression is high.

关 键 词：虚寒状态 药物代谢酶CYP3A 转运蛋白P-gp 大鼠 

分 类 号：P285.5[天文地球—地图制图学与地理信息工程]