地塞米松、苯巴比妥钠和利多卡因对昆明种小鼠肝P4503A酶的影响

Effect of dexamethasone, phenobarbital and lidocaine on hepatic P450 3A enzyme in Kunming mice

目的 研究地塞米松、苯巴比妥钠和利多卡因预处理的昆明种小鼠 P45 0 3A酶有无诱导作用及其作用机制 .方法 给昆明种小鼠腹腔注射常用量地塞米松、苯巴比妥钠或利多卡因 1wk后 ,观察 MEGX累积排泄量、P45 0 3A酶蛋白含量及其 m RNA表达的改变 .结果 与正常对照组相比 ,地塞米松组小鼠 MEGX累积排泄量增加 35 .0 % (P<0 .0 5 ) ,P45 0 3A酶蛋白含量增加 147.1% (P<0 .0 1) ;苯巴比妥钠小鼠 MEGX累积排泄量增加 2 3.4% (P<0 .0 5 ) ,酶蛋白含量增加 43.6 % (P<0 .0 1) ;各组间 P45 0 3A酶 m RNA表达无明显差别 .结论 地塞米松和苯巴比妥钠对昆明种小鼠肝 P45 03A酶有诱导作用 ,该作用位于转录后水平 ;利多卡因对昆明种小鼠肝 P45 0

AIM To study the induction of dexamethasone,phenobarbital and lidocaine on hepatic P450 3A enzyme in Kunming mice. METHODS After administering ip a non toxic dose of dexamethasone, phenobarbital or lidocaine to Kunming mice for 7 d, the urinary recovery of MEGX, a special lidocaine metabolite catalyzed by hepatic P450 3A enzyme, the content of hepatic P450 3A enzyme and its mRNA expression were analyzed by TDX, ELISA and RT PCR techniques. RESULTS In comparison with mice as control, the urinary recovery of MEGX increased by 35.0% and 23.4% ( P <0.05); and the content of hepatic P450 3A enzyme increased by 147.1% and 43.6% ( P <0.01) in mice pretreated with dexamethasone or phenobarbital, respectively, but not mRNA nor the pretreatment with lidocaine. CONCLUSION The pretreatment with dexamethasone and phenobarbital may induce hepatic P450 3A enzyme, which occurs at post transcription level, but lidocaine did not.