山豆根致大鼠肝损伤对肝细胞色素P450酶的影响  

Influence of Hepatic Injury Caused by Sophorae Tonkinensis Radix et Rhizoma on Cytochrome P450 Enzymes in Rats

作　　者：乔靖怡[1] 金若敏[1] 姚广涛[1] 周璐[1] 甄滢滢 

机构地区：[1]上海中医药大学药物安全评价研究中心,上海201203

出　　处：《中国实验方剂学杂志》2014年第18期170-173,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点基础研究发展计划(973计划)(2009CB522807);国家"重大新药创制"科技重大专项(2009ZX09502-002;2011ZX09301-009)

摘　　要：目的:考察山豆根对大鼠肝细胞色素P450酶药酶亚型活性的影响。方法:Wistar大鼠随机分为正常对照组和山豆根低、高剂量组(1,12 g·kg-1)。给药组每日灌胃给药1次,连续21 d,对照组灌服等体积蒸馏水。于给药21d后处理动物,收集血清,采用全自动生化仪测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)和总胆红素(TB)的水平;计算肝脏指数及观察肝组织病理学变化;采用药物探针法测定大鼠肝脏中细胞色素P450酶(CYP450)亚型CYP1A2,CYP2E1,CYP3A4,CYP2C9和CYP2D6的活性。结果:与正常对照组相比,山豆根高剂量组对肝脏有一定的毒性作用,ALT,ALP值和肝脏指数显著升高(P<0.01),部分动物的肝脏出现点状坏死和炎症细胞浸润。山豆根高、低剂量组除CYP3A4外,对其他酶亚型的活性影响趋向一致。山豆根高剂量组对CYP3A4,CYP2C9和CYP2D6活性具有诱导作用(P<0.05或P<0.01)。结论:高剂量山豆根对CYP3A4,CYP2C9和CYP2D6均有明显的诱导作用,尤其是对CYP3A4的影响。提示山豆根与其他CYP3A4底物的药物合用。Objective：To observe the effect of Sophorae Tonkinensis Radix et Rhizoma （STR） on the activity of cytochrome P450 （CYP450） in rats.Method：Wistar rats were randomly divided into normal control group and STR low dose （1 g ·kg-1） and high dose （12 g ·kg-1） groups.STR 1,12 g·kg-1 groups were treated with STR decoction by intragastrical administration,while the normal control group was given distilledwater of the same volume once a day for 21 consecutive days.The blood was collected after 21 day treatment.The levels of serum alanine aminotransferase （ALT）,aspartate aminotransferase （AST）,alkaline phosphatase （ALP） and total bilirubin （TB） were measured by using automatic biochemical analyzer.The liver weight index was calculated and the pathological changes of hepatic tissues were observed.The activity of the subtype enzymes of CYP450 including CYP1A2,CYP2E1,CYP3A1,CYP2C9 and CYP2D6 of the liver was measured by probe drugs.Result：Compared with the normal control group,the STR high dose group demonstrated certain liver toxicity,including the increased activity of ALT,ALP and liver weight index （P ＜ 0.01）,spotty necrosis and inflammatory cell infiltration in the liver of some animals.The high dose of STR induced the activity of CYP3A4,CYP2C9 and CYP2D6 （P ＜0.05 or P ＜ 0.01）.Compared with low dose of STR,high dose of STR induced more activity of CYP3A4 （P ＜ 0.01）.Conclusion：High dose of STR can induce the activity of CYP3A4,CYP2C9 and CYP2D6,and it is more sensitive to CYP3A4,suggesting that it should pay more attention to the drug interactions when STR is used in the combination with other drugs which also have the effects on CYP3A4.

关 键 词：山豆根 肝损伤 细胞色素P450 

分 类 号：R285.5[医药卫生—中药学]