目的 研究丹參、紅花藥對配伍前后對大鼠肝藥酶亞型CYP1A2、CYP2E1和CYP3A4活性的影響。方法 分別選用咖啡因、氯唑沙宗和咪達(dá)唑侖作為CYP1A2、CYP2E1和CYP3A4的探針?biāo)幬?。將大鼠隨機分為4組，即空白對照組、丹參（1.2 g生藥/kg）組、紅花（0.4 g生藥/kg）組、丹參（1.2 g生藥/kg）+紅花（0.4 g生藥/kg）組，按上述劑量ig給藥7 d。于末次給藥后30 min，尾iv探針?biāo)幬锟Х纫颉⒙冗蛏匙诤瓦溥_(dá)唑侖溶液，在不同的時間點取血進(jìn)行檢測；以甲硝唑為內(nèi)標(biāo)，采用HPLC法檢測探針?biāo)幬锟Х纫颉⒙冗蛏匙诤瓦溥_(dá)唑侖的量，評價各藥物組對大鼠CYP3A4、CYP2E1和CYP1A2活性的影響。結(jié)果 與空白對照組比較，丹參組咖啡因、氯唑沙宗和咪達(dá)唑侖的清除率（CL）有所增強，曲線下面積（AUC）減少，其半衰期（t_1/2）有減少趨勢，但差異均不顯著；紅花組咖啡因和氯唑沙宗的CL有所降低，但差異不顯著，咪達(dá)唑侖的CL顯著降低（P<0.01），氯唑沙宗的AUC增加，但差異不顯著，咖啡因和咪達(dá)唑侖的AUC明顯增加（P<0.05、0.01）；丹參+紅花組咖啡因和氯唑沙宗的CL明顯降低（P<0.05），曲線下面積（AUC）明顯增加（P<0.05），其t_1/2有延長趨勢，但差異不顯著。結(jié)論 丹參、紅花配伍后對CYP450亞型CYP1A2和CYP2E1有抑制作用，這可能是丹參、紅花配伍協(xié)同增效的作用機制之一。

Objective To study the influence of Salviae Miltiorrhizae Radix et Rhizome (SMR) and Carthami Flos (CF) before and after compatibility on activitis of cytochrome P1A2 (CYP1A2), cytochrome P2E1 (CYP2E1), and cytochrome P3A4 (CYP3A4) from rat liver microsomes. Methods Using caffeine, chlorzoxazone, and midazolam as the probe drugs of CYP1A2, CYP2E1, and CYP3A4, the SD rats were randomized divided into four groups:control group, SMR (1.2 g crude drug/kg) group, CF (0.4 g crude drug/kg) group, and SMR (1.2 g crude drug/kg)+CF (0.4 g crude drug/kg) group. According to the above dose, rats were ig given drugs for 7 d. Rats were injected with caffeine, chlorzoxazone, and midazolam solution in tail vein 30 min after the last administration, and the blood was collected at different time points. Metronidazole as internal standard, method has been established to determine the levels of caffeine, chlorzoxazone, and midazolam to evaluate the activities of CYP1A2, CYP2E1, and CYP3A4 by HPLC. Results Compared with control group, SMR increased the clearance rates (CL) of caffeine, chlorzoxazone, and midazolam, reduced the AUC, and t_1/2 was also show a decreasing trend, but the difference was not significant. In CF group, CL of caffeine and chlorzoxazone was decreased, but the difference is not significant. CL of midazolam significantly decreased (P<0.01). AUC of chlorzoxazone increased, but the difference was not significant. AUC of caffeine and midazolam increased significantly (P<0.05 and 0.01). In SMR+CF group, the CL of caffeine and chlorzoxazone decreased significantly (P<0.05), the AUC of caffeine and chlorzoxazone increased significantly (P<0.05), and t_1/2 also showed a decreasing trend, but the difference is not significant. Conclusion Compatibility of SMR and CF has an inhibitive effect on CYP1A2 and CYP2E1 in rats, and it could be one of the mechanisms of "interactive synergy".

國家自然科學(xué)基金資助項目（81573624）；陜西省教育廳資助項目（2013JK0835）