内异消体外对大鼠肝脏CYP450酶活性的影响

In Vitro Evaluation of Effect of “Neiyixiao” on Hepatic P450 Enzymatic Activity

目的考察内异消体外对大鼠肝微粒体CYP1A2、CYP2E1、CYP3A酶活性的影响。方法以安替比林为内标,按Omura法测定P450的总量,用牛血清白蛋白为标准测定大鼠肝微粒体蛋白含量,采用HPLC同时定量测定孵育体系中3种探针药物咖啡因、氯唑沙宗、硝苯地平的含量,Cocktail探针药物法评价内异消对大鼠体外肝微粒体3种CYP450酶不同亚型活性的影响。结果对照组、给药组咖啡因、氯唑沙宗、硝苯地平半衰期分别为(19.80±4.26)min、(16.63±2.66)min(P>0.05);(26.87±5.25)min、(18.35±8.55)min(P<0.05);(19.17±4.52)min、(29.50±7.43)min(P<0.05)。结论单次给药内异消对这3种酶有不同作用,在与经由上述酶代谢的药物合用时,可能会产生药物相互作用。

OBJECTIVE To study the effects of Neiyixiao on hepatic P450 enzymatic（CYP1A2, CYP2E1, CYP3A） activity in vitro by cocktail probe drugs. METHODS The amount of P450 enzyme were determined with Omura. Protein level was determined by ultraviolet spectrophotometer and bovine serum albumin was the standard substance. An HPLC method was used for the determination of caffeine, chlorzoxazone and nifedipine in the incubation system and the internal standard was antipyrine. The inhibitory effects of Neiyixiao on rat enzyme activities of CYP1A2, CYP3 A and CYP2E1 were evaluated by cocktail probe drugs. RESULTS For the CYP1A2, half-life of the control group and administration group were（19.80±4.26）min and（16.63±2.66）min, respectively, but no significant difference. For the CYP2E1, half-life of the control group and administration group were（26.87±5.25）min and（18.35±8.55）min（P〈0.05）, respectively. For the CYP3 A, half-life of the control group and administration group were（19.17±4.52）min and（29.50±7.43）min（P〈0.05）, respectively. CONCLUSION Administration ＂Neiyixiao＂ by master single test, the results showed that ＂Neiyixiao＂ could interact with some drugs metabolized by the above three enzymes.