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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。
OBJECTIVE: To investigate the effect and molecular mechanism of tripterygium wilfordii compound compatibility on alleviating hepatic toxicity of Tripterygium wilfordii from the perspective of regulation of metabolic enzymes. Methods: The hepatotoxicity dose of Tripterygium wilfordii was screened in SD rats for one month. The rats were treated with tripterygium wilfordii alone or in combination for one month. Gene microarray was used to detect the gene expression profiles of liver in rats. Quantitative real- (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor (PPAR), aromatic receptor (AhR) expression. Results: The toxic dose of Tripterygium wilfordii was 15.6 g crude drug / kg. The results of gene chip showed that Tripterygium wilfordii inhibited CYP2E1, CYP8B1 and CYP2B expression and induced the expression of CYP7A1. Tripterygium Compound can induce metabolic enzymes CYP3A4, CYP2E1, CYP8B1, CYP2B expression. Real-time quantitative PCR results showed that Tripterygium wilfordii inhibited the expression of nuclear receptor CAR, PXR and PPAR, and Tripterygium wilfordii could improve the inhibitory effect of Tripterygium on nuclear receptors. Conclusion: Tripterygium wilfordii compound compatibility can affect nuclear receptors and regulate the expression of metabolic enzymes, which may further regulate the internal and external metabolic processes, which play an attenuating role.