黄连黄芩及配伍诱导对大鼠肝微粒体5种CYP450亚酶活性的影响

探讨黄连和黄芩配伍代谢性相互作用的机制.大鼠连续ig黄连、黄芩及药对提取物7d诱导肝药酶后,采用cocktail探针底物与肝微粒体体外温孵法,通过HPLC同时检测肝微粒体中5种探针底物代谢消除率,评价各给药组对大鼠肝微粒体CYP450酶活性的影响.与空白组相比,黄连对CYP2D6,CYP1A2呈显著抑制作用；黄芩对CYP1 A2,CYP2E1,CYP2C9具有显著抑制作用.黄连、黄芩按1∶1配伍后仅对CYP1 A2显示抑制作用,对CYP2D6,CYP3A4则呈显著的激活作用；而黄连、黄芩按2∶1配伍后对代谢酶的激活作用消失,表现为对CYP1A2,CYP2C9的显著抑制.结果表明黄连与黄芩对P450酶主要表现为抑制作用,二者按一定比例配伍后作用特点发生改变,呈现出激活和抑制的双重性,且与配伍比例相关.推测黄连与黄芩配伍对代谢酶的抑制和诱导作用是其发挥减毒增效作用的原因之一.

Effect of comparability of Coptis chinensis and Scutellaria baicalensis on five sub-enzymatic activities of liver microsomes in rats

To study the mechanism of metabolic interaction between Coptis chinensis and Scutellaria baicalensis.Rats were given C.chinensis and S.baicalensis for 7 days to produce hepatic microsomal enzyme.Cocktail probe substrate and liver microsome in vitro temperature incubation method were adopted.Meanwhile, the metabolic elimination percentages of the five probe substrates were detected with HPLC, in order to evaluate the effect of each administration group on the enzymatic activity of rat liver microsome CYP450.Compared with the blank group, C.chinensis obviously inhibited CYP2D6 and CYP1A2, and S.baicalensis remarkably inhibited CYP1A2, CYP2E1 and CYP2C9.The compatibility of C.chinensis and S.baicalensis with the ratio of 1:1 not only inhibited CYP1A2, but also remarkably activated CYP2D6 and CYP3A4.However, their activation effect disappeared under the ratio of 2:1, and turned into the inhibitory effect on CYP1A2 and CYP2C9.The results showed that C.chinensis and S.baicalensis had an inhibitory effect on CYP450, but their compatibility with certain ratio resulted in double effects of activation and inhibition, which was related to their compatibility ratio.It is speculated that the inhibitory and inducing effects of C.chinensis and S.baicalensis on metabolic enzymes are among causes for their attenuation and synergistic effects.