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加味佛手散及其配伍对大鼠肝脏P450酶活性及肝细胞形态的影响

Keywords: 加味佛手散,配伍,子宫内膜异位症,P450,肝毒性,阿魏酸,川芎嗪,延胡索乙素

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Abstract:

考察加味佛手散及其不同药物组合对大鼠肝脏P450酶活性及肝细胞形态的影响。大鼠灌胃给药4周后处死,制备肝微粒体,采用肝微粒体体外孵育"鸡尾酒"法,HPLC-MS/MS法测定代谢产物,考察各受试组肝脏P450酶活性,HE染色观察用药前后肝组织病理变化。与对照组相比,加味佛手散组CYP1A2,CYP3A4的酶活性显著升高(P<0.05);阿魏酸+川芎嗪组、川芎嗪+延胡索乙素组CYP1A2,CYP2C9,CYP2D6,CYP2E1,CYP3A4的酶活性显著升高(P<0.05);川芎嗪组CYP1A2,CYP2D6,CYP2E1的酶活性显著升高(P<0.05);阿魏酸组CYP3A4的酶活性显著降低(P<0.05)。用药后阿魏酸和川芎嗪组肝细胞形态正常,延胡索乙素组肝小叶界限不清,肝细胞排列紊乱,边缘模糊,细胞核大小不均,炎细胞浸润。阿魏酸+延胡索乙素、川芎嗪+延胡索乙素、加味佛手散组有炎细胞浸润,但病理变化程度明显较延胡索乙素组轻微,其中加味佛手散组最轻。研究结果表明加味佛手散对大鼠肝脏的CYP1A2,CYP3A4的酶活性具有诱导作用,川芎嗪可能是加味佛手散对CYP1A2产生诱导作用的效应物质。配伍阿魏酸、川芎嗪后可降低延胡索乙素对大鼠肝脏的毒性作用。

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