目的 比较丹参-红花组分配伍对不同性别大鼠肝药酶亚型CYP1A2、CYP2E1和CYP3A4的影响。方法 取SD大鼠按不同性别随机分为丹参-红花高、低剂量（生药4、2 g/kg）组及模型组和对照组，ip盐酸异丙肾上腺素制备心肌缺血模型，丹参-红花高、低剂量组给予相应提取物，模型、对照组给予等体积的蒸馏水，连续ig给药21 d后，取肝组织剪碎制备微粒体，加入非那西丁、氯唑沙宗、睾酮分别作为CYP1A2、CYP2E1和CYP3A4的特异性探针底物，体外温孵育，建立高效液相色谱（HPLC）法检测探针底物浓度，测定CYP1A2、CYP2E1和CYP3A4活性。结果 ①雄性大鼠实验结果显示，与对照组比较，模型组显著抑制CYP2E1和CYP3A4的活性（P<0.05、0.01）；与模型组比较，丹参-红花高剂量组显著抑制CYP2E1和CYP3A4的活性（P<0.05、0.01）；低剂量组显著抑制CYP2E1的活性（P<0.05），诱导CYP3A4（P<0.01）。②雌性大鼠实验结果显示，与对照组比较，模型组显著抑制CYP2E1和CYP3A4的活性（P<0.05），对CYP1A2的影响不显著；与模型组比较，丹参-红花高剂量组显著抑制CYP1A2、CYP2E1和CYP3A4的活性（P<0.05、0.01）；丹参-红花低剂量组抑制CYP2E1的活性（P<0.05），对CYP1A2和CYP3A4的影响不显著。③实验结果对比显示，丹参-红花对雄性、雌性大鼠肝药酶亚型的影响相同点是均抑制了CYP2E1和CYP3A4活性，尤其对CYP2E1的抑制作用比较明显；不同点是丹参-红花低剂量诱导了雄性大鼠CYP3A4活性，但对雌性大鼠CYP3A4活性无明显影响。结论 丹参-红花组分配伍对不同性别大鼠部分肝药酶亚型活性的影响存在一定的差异。

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.

国家自然科学基金委项目（81573624）；陕西省教育厅资助项目（2013JK0835）