淫羊藿次苷Ⅱ对小鼠细胞色素P450酶的影响

Effects of icarisideⅡon hepatic cytochrome P450 expression in mice

目的探究淫羊藿次苷Ⅱ(ICSⅡ)对小鼠细胞色素P450(CYP450)总酶及其主要亚型的影响。方法雄性C57BL/6小鼠随机分为6组:空白对照组(Normal saline,NS)、ICSⅡ(5、10、20 mg/kg组)、地塞米松(Dexamethasone,DEX)80 mg/kg和红霉素(Erythromycin,ERY)200 mg/kg组(n=12)。连续灌胃给药14 d,每天1次,空白对照组给予同等体积的生理盐水。同种方式给予DEX和ERY选择性诱导和抑制小鼠CYP3A11作为对照。采用酶联免疫试剂盒(Elisa kit)检测CYP450总酶的变化情况,血清生化指标(ALT、AST)与HE染色观察ICSⅡ对小鼠的肝脏毒性。蛋白免疫印迹(WB)检测CYP450主要亚型的表达情况。结果ICSⅡ显著抑制CYP450总酶;WB结果显示ICSⅡ显著抑制CYP3A11和诱导CYP1A2亚型的表达;ALT、AST与HE结果显示ICSⅡ无明显肝脏毒性。结论本研究表明ICSⅡ可降低小鼠肝脏微粒体CYP450总酶含量,并抑制其亚型CYP3A11和诱导CYP1A2的表达。

Objective To investigate the effects of icarisideⅡ(ICSⅡ)on the contents of hepatic cytochrome P450(CYP450)enzymes and its major isoforms expressions in mice.Methods Male C57BL/6 mice were randomly divided into six groups:normal saline(NS),ICSⅡ(5,10 and 20 mg/kg)groups,dexamethasone(DEX,80 mg/kg)and erythromycin(ERY,200 mg/kg)groups(n=12).Mice were treated with different doses of ICSⅡby gavage daily for 14 days,and the NS group was administered with volume-matched saline.To induce and inhibit selectively certain CYP3A11,mice were oral gavage with either DEX and ERY,respectively.The contents of CYP450 enzymes in liver were detected by Elisa kits.Liver injury were evaluated by analyzing the histopathological changes and the level of serum biochemical parameters was detected by hematoxylin and eosin staining and Elisa kits.Western blot assay was used to analyze the expression of major CYP450 isoforms.Results ICSⅡdecreased the content of liver CYP450 enzymes.Furthermore,ICSⅡdecreased CYP3A11 and induced CYP1A2 protein expression.No obvious changes in serum and liver tissue biochemical parameters were found and no significant pathological changes were observed in liver tissues after ICSⅡtreatment.Conclusion The present study indicates that ICSⅡcould decrease the content of liver CYP450 enzymes and decrease the expression of CYP3A11 and increase the expression of CYP1A2.