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目的:本文探讨了D-异苯环戊胺对大鼠肝脏细胞色素P450(Cytochrome P450,CYP450)酶活性的抑制和诱导作用。方法:采用探针底物法,通过考察D-异苯环戊胺在体外温孵体系中对大鼠肝微粒体CYP1A1/2,2C6,2D1/2,2E1和3A1/2的IC50值评价其对各亚型的抑制作用。通过考察大鼠连续灌胃10 d后肝微粒体中CYP1A1/2和CYP3A1/2活性的变化评价其诱导作用。结果:D-异苯环戊胺对大鼠肝微粒体CYP2C6和CYP2D1/2的IC50分别为5.3和2.3μmol·L-1,对分别以睾酮和咪达唑仑为底物时CYP3A1/2的IC50分别为8.3和1.7μmol·L-1。30和100 mg·kg-1剂量D-异苯环戊胺连续灌胃给药10 d后,大鼠肝脏CYP1A1/2和CYP3A1/2酶活性为空白对照组的2倍以上。结论:D-异苯环戊胺对大鼠肝微粒体CYP2C6,CYP2D1/2和CYP3A1/2表现出中等强度的抑制作用,对CYP1A1/2和CYP3A1/2有一定的诱导作用。
OBJECTIVE: This study explored the inhibition and induction of D-isopentencyclopentamine on the enzymatic activity of rat liver cytochrome P450 (CYP450). Methods: The IC50 values of CYP1A1 / 2, 2C6, 2D1 / 2, E2E1 and 3A1 / 2 in rat liver microsomes were evaluated by probe substrate method Inhibition of each subtype. The induction of CYP1A1 / 2 and CYP3A1 / 2 activity in liver microsomes was evaluated after 10 days of continuous gavage. Results: The IC50 of D-isopentenylcycline for rat liver microsomes CYP2C6 and CYP2D1 / 2 were 5.3 and 2.3 μmol·L-1, respectively. For CYP3A1 / 2 with testosterone and midazolam as substrates The IC50 were 8.3 and 1.7μmol · L-1.30 and 100 mg · kg-1 D-isocyclopentanamine administration after 10 days of continuous administration, the rat liver CYP1A1 / 2 and CYP3A1 / 2 activity was Blank control group more than 2 times. CONCLUSION: D-isopentenylamine inhibits the liver microsomes CYP2C6, CYP2D1 / 2 and CYP3A1 / 2 to a moderate extent and induces CYP1A1 / 2 and CYP3A1 / 2 to some extent.