目的 研究阿司匹林聯(lián)用華法林對(duì)肝藥物代謝酶CYP3A4活性的影響及其機(jī)制。方法 不同質(zhì)量濃度的阿司匹林、華法林及聯(lián)合用藥處理HepG2細(xì)胞48 h，采用MTT法檢測(cè)細(xì)胞存活率；通過(guò)熒光素酶報(bào)告基因技術(shù)檢測(cè)各組對(duì)PXR轉(zhuǎn)錄酶活性和酶CYP3A4活性的影響；采用熒光定量PCR法和Western blotting法檢測(cè)HepG2細(xì)胞的酶CYP3A4的mRNA和蛋白表達(dá)水平。結(jié)果 與對(duì)照組比較，阿司匹林組、聯(lián)合用藥組細(xì)胞的孕烷X受體（PXR）轉(zhuǎn)錄酶活性、酶CYP3A4活性均顯著降低（P<0.01），CYP3A4 mRNA和蛋白表達(dá)水平顯著降低（P<0.05、0.01），華法林組均無(wú)顯著差異。結(jié)論 阿司匹林聯(lián)用華法林能夠抑制藥物代謝酶CYP3A4活性，其機(jī)制可能是通過(guò)抑制PXR受體的mRNA和蛋白表達(dá)實(shí)現(xiàn)的。

Objective To study the effects of aspirin combined with warfarin on CYP3A4 and its mechanism. Methods HepG2 cells were treated with different concentrations of aspirin, warfarin and its combine for 48 h. cell survival rate was determined by MTT method. The transcriptional activation of PXR and activities of CYP3A4 were detected by luciferase reporter gene technique. The expressions of CYP3A4 mRNA and protein in HepG2 cells were detected by PCR and Western blotting method. Results Compared with the control group, the transcriptional activation of PXR and activity of CYP3A4 in aspirin group and combined groups were significant decreased (P<0.01), and the expressions of CYP3A4 mRNA and protein in HepG2 cells were significant decreased (P<0.05, 0.01), but there were no differences in warfarin group. Conclusion Aspirin combined with warfarin can inhibit the activity of drug metabolizing enzyme CYP3A4, which may be related to inhibition of the expressions of mRNA receptor PXR and protein.