泽泻汤对高脂血症模型小鼠CYP450酶亚型的影响

Effects of Zexie Decoction on CYP450 enzyme subtype in hyperlipidemia model mice

目的探究泽泻汤及其拆方对高脂血症模型小鼠细胞色素P450(CYP450)酶亚型的影响。方法通过给KM小鼠饲喂高脂饲料建立高脂血症模型,将造模成功的小鼠随机分为模型组、泽泻汤组、泽泻组和白术组,并设置空白组,每组10只。泽泻汤组、泽泻组、白术组小鼠每天灌胃给药(给药剂量分别为12.0、8.6、3.4 g·kg^(-1))持续28 d,空白组、模型组均给予等体积生理盐水。采用“Cocktail”探针药物法和实时荧光定量PCR技术检测CYP1A2、CYP2E1、CYP2C9、CYP3A4酶活性及基因表达量。结果与模型组相比,泽泻汤组、泽泻组和白术组CYP3A4酶活性升高,CYP2E1酶活性降低,泽泻汤组CYP1A2酶活性降低。与模型组相比,泽泻汤组、泽泻组和白术组回调了CYP1A2、CYP3A4 mRNA表达水平,对CYP2C9无明显作用,泽泻汤组降低了CYP2E1 mRNA表达水平。结论泽泻汤及其拆方能够回调高脂血症引起的CYP3A4酶活性及基因表达量的改变,而泽泻在泽泻汤中起主导作用。

Objective To explore the effects of Zexie Decoction and its disassembled prescriptions on CYP450 enzyme subtype in hyperlipidemia model mice.Methods Hyperlipidemia model was established by feeding KM mice with high fat diet.The model mice were randomly divided into model group,Zexie Decoction group,Rhizoma alismatis group and Atractylodes macrocephala Koidz group,and set blank groups with 10 animals in each group.The mice in the Zexie Decoction group,Rhizoma alismatis group and Atractylodes macrocephala Koidz group were administered by gavage once a day(administration doses were 12.0,8.6,3.4 g·kg^(-1),respectively)for 28 consecutive days,the blank group and model group were given the same volume of normal saline.The enzymatic activity and gene expression levels of CYP1A2,CYP2E1,CYP2C9 and CYP3A4 were detected by"Cocktail"probe drug method and real-time fluorescence quantitative PCR.Results Compared with the model group,the CYP3A4 enzymatic activity in the Zexie Decoction group,Rhizoma alismatis group and Atractylodes macrocephala Koidz group were increased,CYP2E1 enzymatic activity was decreased,while CYP1A2 enzymatic activity in Zexie Decoction group were decreased.Compared with the model group,the mRNA expression levels of CYP1A2 and CYP3A4 in the Zexie Decoction group,Rhizoma alismatis group and Atractylodes macrocephala Koidz group were reversed,but had no significant effect on CYP2C9,while the mRNA expression level of CYP2E1 was decreased in Zexie Decoction group.Conclusion Zexie Decoction and its disassembled prescriptions can reverse the changes of enzymatic activity and gene expression of CYP3A4 caused by hyperlipidemia,Rhizoma alismatis plays a leading role in Zexie Decoction.