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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 investigate the changes of drug metabolizing enzyme CYP3A and transporter P-gp under the condition of Deficiency of Cold through in vitro and in vivo experiments. Methods The hypoxia model rats were intramuscularly injected with cortisone (20 mg / kg) intraperitoneally for 14 days to observe the activity of CYP3A in liver and small intestine and the level of P-gp protein in small intestine in normal and asthenic rats. L02 cells and Caco-2 cells were used as the cell model to interfere with normal and Deficiency rat serum separately. The activity of CYP3A in L02 cells and the level of P-gp protein in Caco-2 cells were observed. Results The activity of CYP3A in liver and small intestine of rats with asthenia cold decreased significantly (P <0.05), while the expression of P-gp in small intestine decreased significantly (P <0.05). The activity of CYP3A in L02 cells was significantly decreased (P <0.05), but there was no significant change in P-gp protein level in Caco-2 cells. Conclusions Both in vitro and in vivo experiments verify that CYP3A activity is in a low state during the cold phase. P-gp does not change in Caco-2 cells, which may be related to Caco-2 cell line itself and high expression of P-gp.