隐丹参酮对大鼠肝微粒体CYP酶的影响  

Effects of Cryptotanshinone on Cytochrome P450 Isoforms in Rat Liver Microsomes

作　　者：潘莹[1,2] 邓颖[2,3] 毕惠嫦[2] 黄民[2] 

机构地区：[1]华南肿瘤学国家重点实验室,中山大学肿瘤防治中心,广州510060 [2]中山大学临床药理研究所,广州510080 [3]深圳市宝安人民医院,广东深圳518101

出　　处：《中药新药与临床药理》2009年第4期331-334,共4页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省关键领域重点项目(2003A30904)

摘　　要：目的研究隐丹参酮(CTS)对大鼠肝微粒体CYP酶各亚型的影响。方法取SD大鼠,按体重随机分为6组,每组3只,隐丹参酮各剂量组分别灌胃给予隐丹参酮20、60、180、540mg/kg,连续10d;阴性对照组,灌胃给予羟丙基环糊精水溶液10mL/kg,连续10d;阳性对照组从实验第7天开始按80mg/kg腹腔注射β-NF,于第10天最后1次给药后将大鼠断头处死,取肝脏制备肝微粒体,分别用Cocktail体外孵育法、蛋白免疫印记及逆转录聚合酶链反应观察CTS对CYP酶各亚型酶活性、蛋白表达及基因表达的影响。结果CTS灌胃后对大鼠肝微粒体CYP1A2有明显的诱导作用,并呈剂量依赖性,CTS20～540mg/kg剂量组CYP1A2探针代谢物的量、蛋白表达及基因表达分别较阴性对照组提高60%～430%、130%～320%及10%～150%;隐丹参酮对CYP酶其他亚型无明显作用。结论CTS能显著地诱导大鼠肝微粒体CYP1A2,提示经CYP1A2代谢的药物在临床上与CTS合用时,可能发生药物之间的相互作用。Objective To observe the effects of cryptotanshinone （CTS） on cytochrome P450 （CYP） isoforms in the rat liver microsomes. Method The rats were randomized into six groups according to the body weight, 3 rats in each group. CTS groups were treated with CTS at the doses of 20 -540 mg/kg per day for 10 days, and the negative control group was treated with 10 mL/kg hydroxylpropyl - β - cyclodextrin solution. The positive group was injected with β - NF（80 mg/kg） intraperitoneally on the 7th day, and all the animals were sacrificed by decapitation on the 10th day after last dose. The liver was got out for the preparation of liver microsomes. The activities of six kinds of CYP isoforms were detected by cocktail in -vitro incubation method. Besides, the expression level of CYP isoforms mRNA and protein in rat liver was analyzed by reverse transcription polymerase chain reaction （RT -PCR） and western -blotting assay, respectively. Results CTS significantly increased the activity of CYP1A2 in a dose - dependent manner. In CTS groups at the dosages of 20 - 540 mg/kg, the activity of CYP1A2 was 60 % -430 % higher, CYP1A2 protein expression level was 130 % -320 % higher, and CYP1A2 mRNA expression level was 10 % - 150 % higher than that of the negative control group. CTS had no effect on other kinds of CYP isoforms. Conclusion CTS can induce hepatic microsome CYP1A2 expression significantly, which indicates potential diug- drug interaction might occured when CTS is co - administrated with those drugs metabolized by CYP1A2.

关 键 词：隐丹参酮 药物相互作用 肝微粒体 细胞色素P450酶 

分 类 号：R285.5[医药卫生—中药学]