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目的研究苯环喹溴铵对大鼠肝脏CYP450酶是否有诱导作用。方法将SD大鼠,分为空白溶剂组、阳性对照组和苯环喹溴铵低中高剂量给药组(分别鼻腔给予苯环喹溴铵生理盐水溶液1,3或9 mg·kg-1),分别于连续给药后处死,取肝称重并制备微粒体。计算大鼠肝脏脏器系数;测定大鼠肝脏微粒体CYP450蛋白含量;通过HPLC-MS/MS测定大鼠肝微粒体温孵体系中6β-羟基睾酮和对乙酰氨基酚的浓度;应用底物法测定大鼠肝微粒体CYP1A1/2和CYP3A1/2酶的活性。结果阳性对照组与空白溶剂组相比,在大鼠肝脏脏器系数、CYP450蛋白含量及CYP1A1/2和CYP3A1/2酶活性上均有增加,且具有显著性差异(P<0.05)。苯环喹溴铵低中高剂量给药组与空白溶剂组在肝脏脏器系数、CYP450蛋白含量和CYP1A1/2酶活性上均无显著性差异(P>0.05);苯环喹溴铵低中高剂量给药组大鼠肝脏CYP3A1/2酶的活性未高于空白溶剂组。结论阳性对照组对大鼠肝脏CYP450酶有诱导作用,所建立的实验体系可用于诱导作用的评价;苯环喹溴铵低中高3个剂量组对大鼠肝脏CYP450酶均无诱导作用。
OBJECTIVE To study whether benzocyclopurine induces CYP450 activity in rat liver. Methods Sprague Dawley rats were divided into blank solvent group, positive control group and low, medium and high dose of phenylcyclohexaazolinium bromide group (nasal cavity was given 1, 3 or 9 mg · kg-1) , Were sacrificed after continuous administration, liver weight and microsomes were prepared. The liver organ coefficient of rat liver was calculated. The content of CYP450 protein in rat liver microsome was determined. The concentration of 6β-hydroxytestosterone and acetaminophen in rat liver microsomal incubation system was determined by HPLC-MS / MS. Activity of rat liver microsomal CYP1A1 / 2 and CYP3A1 / 2 enzymes. Results Compared with the blank solvent group, the positive control group showed an increase in liver organ coefficient, CYP450 protein content and CYP1A1 / 2 and CYP3A1 / 2 enzyme activities (P <0.05). There was no significant difference in liver organ coefficient, CYP450 protein content and CYP1A1 / 2 enzyme activity between the low, medium and high doses of Benazidone bromide group and the blank solvent group (P> 0.05) The activity of CYP3A1 / 2 enzyme in the liver of the administration group was not higher than that of the blank solvent group. Conclusion The positive control group can induce rat hepatic CYP450 enzyme. The established experimental system can be used to evaluate the induction effect. The low, middle and high doses of 3-phenylbenzuronium bromide have no effect on the hepatic CYP450 enzyme.