雷公藤复方配伍对大鼠肝脏代谢酶基因表达的影响

目的:从调控代谢酶角度探讨雷公藤复方配伍减轻雷公藤肝脏毒性的作用及分子机制。方法:SD大鼠给药1个月筛选雷公藤的肝毒性剂量;雷公藤单药和复方分别ig给药大鼠1个月,基因芯片检测大鼠肝脏基因表达谱,实时定量聚合酶链式反应(PCR)技术检测核受体组成型雄甾烷受体(CAR),孕烷X受体(PXR),过氧化物酶体增殖剂激活受体(PPAR),芳香烃受体(AhR)的表达。结果:雷公藤肝毒性剂量为15.6 g生药/kg;基因芯片结果显示,雷公藤可抑制细胞色素P450酶(CYP)2E1,CYP8B1,CYP2B等表达,诱导CYP7A1的表达。雷公藤复方可诱导代谢酶CYP3A4,CYP2E1,CYP8B1,CYP2B等表达。实时定量PCR结果显示,雷公藤可抑制核受体CAR,PXR,PPAR基因表达,雷公藤复方可改善雷公藤对核受体的抑制作用。结论:雷公藤复方配伍可影响核受体,调控代谢酶的表达,这可能进而调节内外源代谢过程,从而起到减毒作用。

Effect of Compound Tripterygium wilfordii on Expressions of Metabolic Genes in Rat Livers

Objective: To study the effect and mechanism of compound Tripterygium wilfordii(TW) on attenuating hepatotoxicity through regulation of metabolic enzymes. Method: Sprague dawley (SD) rats were intragastrically administrated with different doses of TW for one month to screen the dose of hepatotoxicity. TW single drug and compound TW were intragastrically administrated for one month respectively. Gene expression changes in rat liver were detected using gene chip technique, and expressions of constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferators-activated receptors (PPARs) and aryl hydrocarbon receptor (AhR) were detected using real-time quantitative PCR. Result: Hepatotoxicity dose was 15.6 g·kg^-1 of raw TW. Gene chip results showed that TW could inhibit expressions of cytocharome P450 enzymes(CYP) 2E1, CYP8B1 and CYP2B, and induce expression of CYP7A1.Compound TW could induce expressions of CYP3A4, CYP2E1, CYP8B1, and CYP2B. Real-time quantitative PCR results showed that TW could inhibit expressions of nuclear receptors CAR, PXR and PPAR, and Compound TW could improve its inhibitory effect on nuclear receptors. Conclusion: Compound TW preparations can affect expressions of nuclear receptors and metabolic enzymes, which may regulate endogenous and exogenous metabolic processes and thereby attenuate hepatotoxicity.