Farrell G C, Zaluzny L
Aust J Exp Biol Med Sci. 1984 Jun;62 ( Pt 3):291-301. doi: 10.1038/icb.1984.29.
In order to determine whether non-specific defects of protein synthesis account for reduced levels of cytochrome P-450 in cirrhotic liver, total microsomal protein synthesis and response to microsomal enzyme-inducing agents have been examined in rats. Cirrhosis was produced by administration of carbon tetrachloride (CCl4) and phenobarbitone for 10 weeks. Ten days after stopping these agents, cytochrome P-450 levels were 30% lower in cirrhotic liver than in controls (p less than 0.0001). However, total microsomal protein synthesis, determined in vivo by administration of [3H]-leucine, was similar in cirrhotic (1347 +/- 420 dpm/mg protein) and control (1317 +/- 303 dpm/mg protein) liver. Three separate types of microsomal enzyme-inducing agents, phenobarbitone, beta-naphthoflavone, and pregnenolone 16 alpha-carbonitrile, were administered to cirrhotic and normal rats. In both groups of animals increases of total cytochrome P-450 and selective changes of cytochrome P-450 isoenzymes (assessed by mixed function oxidase activity towards four substrates) were qualitatively and quantitatively similar. It is concluded that hepatocytes of cirrhotic rat liver synthesize microsomal protein at a normal rate but less of it is cytochrome P-450, and the entire process of enzyme induction is intact. Thus, it appears likely that altered regulation of basal levels of cytochrome P-450 rather than an altered response of the liver is responsible for the lowered cytochrome P-450 content of cirrhotic rat liver.
为了确定蛋白质合成的非特异性缺陷是否导致肝硬化肝脏中细胞色素P - 450水平降低，研究人员检测了大鼠肝微粒体的总蛋白合成以及对微粒体酶诱导剂的反应。通过给予四氯化碳（CCl4）和苯巴比妥10周诱导大鼠肝硬化。停用这些药物10天后，肝硬化肝脏中细胞色素P - 450水平比对照组低30%（p小于0.0001）。然而，通过给予[3H] - 亮氨酸在体内测定的肝微粒体总蛋白合成，在肝硬化肝脏（1347±420 dpm/mg蛋白）和对照肝脏（1317±303 dpm/mg蛋白）中相似。分别给肝硬化大鼠和正常大鼠施用三种不同类型的微粒体酶诱导剂：苯巴比妥、β - 萘黄酮和孕烯醇酮16α - 腈。在两组动物中，总细胞色素P - 450的增加以及细胞色素P - 450同工酶的选择性变化（通过对四种底物的混合功能氧化酶活性评估）在定性和定量上相似。得出的结论是，肝硬化大鼠肝脏的肝细胞以正常速率合成微粒体蛋白，但其中细胞色素P - 450较少，并且酶诱导的整个过程是完整的。因此，肝硬化大鼠肝脏中细胞色素P - 450含量降低似乎可能是由于细胞色素P - 450基础水平的调节改变，而不是肝脏反应的改变。
