首页|淫羊藿次苷Ⅱ对小鼠细胞色素P450酶的影响

淫羊藿次苷Ⅱ对小鼠细胞色素P450酶的影响

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目的 探究淫羊藿次苷Ⅱ(ICS Ⅱ)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)、ICS Ⅱ(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ICS Ⅱ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 ICS Ⅱ显著抑制CYP450总酶;WB结果显示ICS Ⅱ显著抑制CYP3 A11和诱导CYP1A2亚型的表达;ALT、AST与HE结果显示ICS Ⅱ无明显肝脏毒性.结论 本研究表明ICS Ⅱ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.
Effects of icariside Ⅱ on hepatic cytochrome P450 expression in mice
Objective To investigate the effects of icariside Ⅱ (ICS Ⅱ) 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),ICS Ⅱ (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 ICS Ⅱ by garage 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 ICS Ⅱ decreased the content of liver CYP450 enzymes.Furthermore,ICS Ⅱ decreased 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 ICS Ⅱ treatment.Conclusion The present study indicates that ICS Ⅱ could decrease the content of liver CYP450 enzymes and decrease the expression of CYP3A11 and increase the expression of CYP1A2.

icariside ⅡCYP450flavonoidsliver toxicity

刘木波、高健美、石京山、余昌胤、龚其海

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遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563099

遵义医科大学药学院,贵州遵义563099

遵义医科大学附属医院神经内科,贵州遵义563099

淫羊藿次苷Ⅱ 细胞色素P450 黄酮 肝脏毒性

贵州省科技创新人才团队建设项目贵州省百级高层次创新人才项目石京山药理学导师工作室项目长江学者和创新团队发展计划遵义医科大学优秀青年人才项目

20154023QKHRCPT20165684GZS-201607IRT_17R11315zy-002

2019

遵义医学院学报
遵义医学院

遵义医学院学报

CSTPCD
影响因子:0.692
ISSN:1000-2715
年,卷(期):2019.42(5)
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