目的 比較丹參-紅花組分配伍對不同性別大鼠肝藥酶亞型CYP1A2、CYP2E1和CYP3A4的影響。方法 取SD大鼠按不同性別隨機(jī)分為丹參-紅花高、低劑量（生藥4、2 g/kg）組及模型組和對照組，ip鹽酸異丙腎上腺素制備心肌缺血模型，丹參-紅花高、低劑量組給予相應(yīng)提取物，模型、對照組給予等體積的蒸餾水，連續(xù)ig給藥21 d后，取肝組織剪碎制備微粒體，加入非那西丁、氯唑沙宗、睪酮分別作為CYP1A2、CYP2E1和CYP3A4的特異性探針底物，體外溫孵育，建立高效液相色譜（HPLC）法檢測探針底物濃度，測定CYP1A2、CYP2E1和CYP3A4活性。結(jié)果 ①雄性大鼠實(shí)驗(yàn)結(jié)果顯示，與對照組比較，模型組顯著抑制CYP2E1和CYP3A4的活性（P<0.05、0.01）；與模型組比較，丹參-紅花高劑量組顯著抑制CYP2E1和CYP3A4的活性（P<0.05、0.01）；低劑量組顯著抑制CYP2E1的活性（P<0.05），誘導(dǎo)CYP3A4（P<0.01）。②雌性大鼠實(shí)驗(yàn)結(jié)果顯示，與對照組比較，模型組顯著抑制CYP2E1和CYP3A4的活性（P<0.05），對CYP1A2的影響不顯著；與模型組比較，丹參-紅花高劑量組顯著抑制CYP1A2、CYP2E1和CYP3A4的活性（P<0.05、0.01）；丹參-紅花低劑量組抑制CYP2E1的活性（P<0.05），對CYP1A2和CYP3A4的影響不顯著。③實(shí)驗(yàn)結(jié)果對比顯示，丹參-紅花對雄性、雌性大鼠肝藥酶亞型的影響相同點(diǎn)是均抑制了CYP2E1和CYP3A4活性，尤其對CYP2E1的抑制作用比較明顯；不同點(diǎn)是丹參-紅花低劑量誘導(dǎo)了雄性大鼠CYP3A4活性，但對雌性大鼠CYP3A4活性無明顯影響。結(jié)論 丹參-紅花組分配伍對不同性別大鼠部分肝藥酶亞型活性的影響存在一定的差異。

Objective To compare the effect of the activity of drug-metabolism enzymes caused by the compatibility of Salvia miltiorrhiza and Carthamus tinctorius in male and female rats with myocardial ischemia. Methods SD rats were respectively divided into four groups according to different genders:control group, model group, CSC high and low dose (4 and 2 g/kg) groups. Myocardial ischemia model was prepared by ip isoprenaline hydrochloride. Rats were ig administered respectively with distilled water or equal volume of Salvia miltiorrhiza and Carthamus tinctorius extract for consecutive 21 d. Liver tissue was cut for microsomal preparation, and phenacetin, chlorzoxazone and testosterone were used as specific probes of CYP2E1, CYP1A2 and CYP3A4 for in vitro incubation. A high performance liquid chromatography (HPLC) method was established to detect the probe substrate concentration and determine the activities of CYP1A2, CYP2E1, and CYP3A4. Results ① In male rats, compared with control group, the activities of CYP2E1 and CYP3A4 were significantly inhibited in model groups (P < 0.05 or 0.01); Compared with model group, the activities of CYP2E1 and CYP3A4 were significantly inhibited in CSC high dose groups (P < 0.05 or 0.01), the activities of CYP2E1 were significantly inhibited in low dose groups (P < 0.05), and the activities of CYP3A4 were significantly induced in low dose groups (P < 0.01); ② In female rats, compared with control group, the activities of CYP2E1 and CYP3A4 were significantly inhibited in model groups (P < 0.05); Compared with model group, the activities of CYP1A2, CYP2E1, and CYP3A4 were significantly inhibited in high dose groups (P < 0.05 or 0.01), and the activities of CYP2E1 were significantly inhibited in low dose groups (P < 0.05); ③ According to the results of the experiment in male and female rats, the similarity of the effect of Salvia miltiorrhiza and Carthamus tinctorius on the activity of drug-metabolism enzymes in male and female rats was that the activities of CYP2E1 and CYP3A4 were all significantly inhibited in high dose groups, which was especially obvious for CYP2E1. The difference was that the activity of CYP3A4 was significantly induced in male rats, while that was not affected in female rats. Conclusion The activity of drug-metabolism enzymes induced or inhibited by Salvia miltiorrhiza and Carthamus tinctorius extract is different between male and female rats.

國家自然科學(xué)基金委項(xiàng)目（81573624）；陜西省教育廳資助項(xiàng)目（2013JK0835）