Anaerobic halothane Dehalogenation in extra hepatic organe and Enzyme induction and Enzyme Inhibition.

本文研究了氟烷麻醉后肝脏和肝外微粒体内巴比妥盐预处理的影响，2)抑制氟烷厌氧脱卤化的作用，以及3)肝外氟烷厌氧脱卤化的影响。用雄性Wistar大鼠研究了5种巴比妥类药物在体预处理对大鼠肝微粒体电子传递系统的诱导和对氟烷厌氧脱氢体外活性的影响。预先给予苯巴比妥、硫喷妥钠、胸腺嘧啶和戊巴比妥、P450、b5和Fp2，可使细胞数量和活性增加。递增效应从大到小排列如下：苯巴比妥、硫喷妥钠、胸腺醛和戊巴比妥。赛可巴比妥没有显示出任何效果。苯巴比妥、硫喷妥钠和胸腺嘧啶醛可显著降低肝微粒体和…中卤代糖的厌氧脱卤化活性此外，苯胺羟化活性也降低。采用大鼠肝微粒体组分，体外研究了镇痛剂对氟烷厌氧脱氢的抑制作用。氟烷、氯二氟乙烷和三氟氯乙烷厌氧脱卤化的抑制常数由大到小依次为：吗啡(656µM，2570µM)、氯丙嗪(49.7µM，68.1µM)、氯胺酮(24.9µM，64.4µM)、芬太尼(23.9µM，34.1um)、羟基锌(19.2µM，50µM)、安定(17.0muM，13.9muM)、旁丙啡(11.2muM，22.4muM)和五氮唑啉(1.96muM，6.67muM)。本文研究了氟烷在兔肝、肾、肺微粒体中的厌氧脱卤活性。肝脏、肾脏和肺中的P450分别为1.91、0.19和0.42nmol/mg蛋白。肝、肾和肺的CDE形成活性分别为0.39、0.38和0.08nmol/nmolp450/min，CTE形成活性分别为0.67、0.59和0.22nmol/nmolp450/min。在体实验中，苯巴比妥可使肝脏和肾脏中P450的含量分别增加到2.95(154%)和0.40(211%)nmol/mg蛋白，但对肺的影响不大。苯巴比妥可使小鼠肝脏和肾脏的CDE形成活性分别增加到0.53(138%)和0.70(185%)nmol/nmolp450/min，但对肺的影响不大。肝、肺CTE形成活性变化不大，肾脏CTE形成活性下降至0.33(56%)nmolp450/min。较少

Hepatic disorder following halothane anesthesia were studied in the liver and extrahepatic microsomes with regard to 1)effects of in vivo pretreatment of barbiturates, 2)inhibitory effects on anaerobic dehalogenation of halothane and 3)extrahepatic anaerobic dehalogenation of halothane.1. Effects of in vivo pretreatment of five barbiturates on induction of electron transport system of rat liver microsomes and on the in vitro activity of the anaerobic dehelogenation of halothane were studied in male Wister rats. Preadministration of Phenobarbital, thiopental, thyamalal and pentobarbital, p450 and b5 and fp2 brought about increase in amount and activity. The incremental effects could be arranged in the following order from large to small: phenobarbital, thiopental, thyamylal and pentobarbital. secobarbital did not show any effect. Pretreatment of phenobabital, thiopental and thyamylal significantly reduced the activity of anaerobic dehalogenation of halothame in the liver microsomes and … More also reduced activity of hydroxylation of aniline.2. Inhibitory effects on anaerobic dehelogenation of halothane by analgesic agents was investigated in vitro using rat liver microsomal fraction. The inhibitor constant for anaerobic dehalogenation of halothane, chlorodifluoroetylene(CDE) and chlorotrifluoroethane(CTE) formation could be arranged in the following order from large to small: morphine(656muM,2570muM), chlorpromazine(49.7muM,68.1muM), ketamine(24.9muM,64.4muM) fentanyl(23.9muM,34.LmuM), hydroxyzine(19.2muM,50.,muM), diazepam(17.0muM,13.9muM), bypurenorphine(11.2muM,22.4muM) and pentazocine(1.96muM,6.67muM).3. Activity of anaerobic dehalogenation of halothane was studied in microsomes of the liver, kidney and lung of rabbits. P450 in the liver, kidney and lung was 1.91,0.19 and 0.42 nmol/mg protein, respectively. The activity of CDE formation in the liver, kidney and lung was 0.39,0.38 and 0.08 nmol/nmolp450/min, respectively, which the activity of CTE formation was 0.67,0.59 and 0.22 nmol/nmolp450/min respectively. In vivo pretreatment of phenobarbital increased the amount of p450 to 2.95(154%)nmol/mg protein in the liver and 0.40(211%)nmol/mg protein in kidney, but little change was induced in the lung. In vivo pretreatment of phenobarbital enhanced the activity of CDE formation in the liver and kidney to 0.53(138%), and 0.70(185%)nmol/nmolp450/min respectively, but little change was observed in the lung. The activity of CTE formation showed little change in the liver and lung, but was decreased to 0.33(56%)nmol/nmolp450/min in the kidney. Less