目的 研究無梗五加果實(shí)提取物對大鼠CYP450亞型CYP1A2、CYP2C19、CYP2E1、CYP3A4活性的影響。方法 以咖啡因、奧美拉唑、氯唑沙宗和咪達(dá)唑侖作為CYP1A2、CYP2C19、CYP2E1和CYP3A4特異性探針?biāo)幬铮渲芻ocktail混合探針溶液，建立同時測定4種探針?biāo)幬镅帩舛鹊母咝б合嗌V法。將SD大鼠隨機(jī)分為無梗五加果實(shí)70%乙醇提取物組、水提取物組和對照組，每天分別ig無梗五加果實(shí)70%乙醇提取物溶液、水提取物溶液和溶劑10 mL/kg，連續(xù)給藥1周，于第8天ip混合探針?biāo)幬?0 mL/kg，分別在給藥0、0.083、0.25、0.417、0.583、0.833、1、2、3、5、8、11、12 h于大鼠眼眶靜脈叢采血，采用HPLC法對血漿樣品進(jìn)行分析，對給藥組和對照組探針?biāo)幬锏乃巹訉W(xué)參數(shù)生物半衰期（t_1/2）進(jìn)行比較。結(jié)果 與對照組比較，無梗五加果實(shí)水提取物組和70%乙醇提取物組咖啡因、咪達(dá)唑侖的t_1/2顯著降低，奧美拉唑、氯唑沙宗的t_1/2顯著增加，差異均具有統(tǒng)計學(xué)意義（P<0.05、0.01）。結(jié)論 無梗五加果實(shí)70%乙醇提取物和水提取物對大鼠的CYP2C19、CYP2E1有抑制作用，對大鼠的CYP1A2、CYP3A4有誘導(dǎo)作用。

Objective To study effects of Acanthopanax sessiliflorus fruit extract on four isoforms of CYP1A2, CYP2C19, CYP2E1, and CYP3A4 activities of CYP450 of rats. Methods Using caffine, omeprazole, chlorzaxazone, and midazolam as the specific probe drugs to make the cocktail probe solution for CYP1A2, CYP2C19, CYP2E1, and CYP3A4, respectively. An HPLC method was established to simultaneously determinate the concentrate of four probe drugs in plasma. Rats were randomly divided into two medicine groups and a control group. They were administrated of 70% ethanol and water extracts of A. sessiliflorus fruit and blank solvent 10 mL/kg for one week. And then they were injected the cocktail solution by abdominal cavity at the eighth day, the blood samples were obtained through the eyeballs extirpating at a series of time-points 0, 0.083, 0.25, 0.417, 0.583, 0.833, 1, 2, 3, 5, 8, 11, and 12 h. The plasma samples were analyzed by HPLC method. The pharmacokinetic parameters half-life (t_1/2) of the probe drugs were compared between the control group and medicine groups. Results Compared with the control group, t_1/2 of caffeine and midazolam in A. sessiliflorus fruit extract water and 70% ethanol extracts groups were notablely shorten, while omeprazole and chlorzoxazone were prominently prolonged, with significant difference between two groups (P<0.05, 0.01). Conclusion The activities of A. sessiliflorus fruit extract water and 70% ethanol extracts on CYP1A2 and CYP3A4 of rats are induced, but on CYP2C29 and CYP2E1 of rats are inhibited.

遼寧省自然科學(xué)基金資助項(xiàng)目（20102147；遼寧中醫(yī)藥大學(xué)優(yōu)秀青年藥學(xué)人才基金項(xiàng)目（yxrc0902）