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

在肝脏和肝外微粒体中研究氟烷麻醉后的肝脏疾病，包括1）巴比妥类药物体内预处理的影响，2）氟烷厌氧脱卤的抑制作用和3）氟烷肝外厌氧脱卤。用雄性Wister大鼠研究了5种巴比妥类药物体内预处理对大鼠肝微粒体电子传递系统的诱导作用和体外氟烷无氧脱卤活性的影响。预先给予苯巴比妥、硫喷妥钠、胸腺嘧啶、戊巴比妥钠、p450、b5和fp 2可使其含量和活性增加。递增效应由大到小依次为苯巴比妥、硫喷妥钠、胸腺嘧啶醛和戊巴比妥。司可巴比妥未显示任何作用。苯巴比妥钠、硫喷妥钠和胸腺嘧啶醛预处理可显著降低肝微粒体中氟烷的厌氧脱卤活性， 关于我们 也降低了苯胺的羟基化活性。2.采用大鼠肝微粒体法研究了镇痛剂对氟烷厌氧脱卤的抑制作用。氟烷厌氧脱卤、氯二氟乙烯（CDE）和氯三氟乙烷（CTE）生成的抑制常数由大到小依次为：吗啡（656 μ M，2570 μ M），氯丙嗪（49.7 μ M，68.1 μ M），氯胺酮（24.9 μ M，64.4 μ M），芬太尼（23.9 μ M，34.1 μ M），羟嗪（19.2 μ M，50.1 μ M），地西泮（17.0 μ M，13.9 μ M）、拜丙诺啡（11.2 μ M，22.4 μ M）和喷他佐辛（1.96 μ M，6.67 μ M）。本文研究了氟烷在家兔肝、肾、肺微粒体中的厌氧脱卤活性。肝、肾、肺中P450分别为1.91、0.19和0.42 nmol/mg蛋白。肝、肾、肺的CDE生成活性分别为0.39、0.38和0.08 nmol/nmolp 450/min，CTE生成活性分别为0.67、0.59和0.22 nmol/nmolp 450/min。在体内苯巴比妥预处理使肝脏中p450的量增加到2.95（154%）nmol/mg蛋白，肾脏中增加到0.40（211%）nmol/mg蛋白，但在肺中几乎没有引起变化。苯巴比妥预处理可使肝、肾CDE生成活性分别提高到0.53（138%）和0.70（185%）nmol/nmolp 450/min，而对肺CDE生成活性影响不大。肝和肺的CTE形成活性变化不大，但肾的CTE形成活性下降至0.33（56%）nmol/nmolp 450/min。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