厚朴酚抑制异丙酚葡萄糖醛酸转移代谢的组织差异研究

Tissue Related Differences with Inhibition of Magnolol on Propofol Glucuronidation

目的为了评价含厚朴酚的中药干预异丙酚在人体内代谢的风险。方法在人肠、肝、肾微粒体体系中,通过动力学分析的方法,在体外探讨了厚朴酚对各微粒体催化异丙酚葡萄糖醛酸转移代谢活性的抑制能力。结果厚朴酚能显著抑制异丙酚在人肝、肾微粒体中的葡萄糖醛酸结合代谢反应,抑制过程均遵循混合抑制动力学模型,抑制常数Ki分别为0.1和0.2μmol·L^(-1)。与人肝、肾微粒体不同,人肠微粒体中异丙酚的葡萄糖醛酸结合代谢不受厚朴酚的影响。结论含厚朴酚的中药,在人整体水平上难以抑制异丙酚葡萄糖醛酸结合代谢路径。

OBJECTIVE To investigate the risk of magnolol interfering into propofol glucuronidation in human. METHODS This study was performed in pooled microsomes from human liver, intestine and kidney （HLM, HIM, HKM, respectively）. Kinetic analyses were conducted to gain the inhibition potentials of magnolol against propofol glucuronidation in HLM, HIM, and HKM. RESULTS Magnolol can potently inhibit propofol glucuronidation in HLM and HKM, following mixed inhibition kinetics with Ki values of 0. 1 and 0. 2 μmol· L - 1 , respectively. Different from HLM and HKM, propofol glucuronidation in HIM was not affected by the presence magnolol. CONCLUSION Magnolol is hardly to depress systemic propofol glucuronidation due to lack of inhibition of the intestinal metabolic pathway.