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目的：研究肝硬化和黄疸患者肝脏中CYP3A4蛋白含量、活性及其mRNA表达，进一步探讨其药理学意义。方法：提取肝炎后肝硬化、阻塞性黄疽及肝血管瘤患者的肝组织标本，以后者为正常肝组织对照；Nash法测定CYP3A4酶活性，ELISA法测定蛋白量，一步法抽提肝组织总 RNA，随机引物标记法制备 CYP3A4 cDNA探针，Northern杂交比较 CYP3A4基因在以上三组中的表达差异。结果：肝炎后肝硬化患者 CYP3A4蛋白量、活性及 mRNA表达较正常肝显著降低（P＜0．01），而阻塞性黄疽患者该酶改变与正常肝相差无显著性。结论：肝硬化患者 CYP3A4 mRNA表达显著降低，导致同工酶含量和酶活性下降，肝脏对包括静脉麻醉药物在内的多种药物的代谢能力下降，提示临床麻醉工作中应考虑药酶改变，减低患者的麻醉药剂量。
Objective: To study the content, activity and mRNA expression of CYP3A4 in the liver of patients with cirrhosis and jaundice, and further explore its pharmacological significance. Methods: Liver samples of patients with cirrhosis, obstructive jaundice and hepatic hemangioma after hepatitis were collected, and the latter was normal liver tissue. The activity of CYP3A4 was determined by Nash method. The protein content was determined by ELISA. RNA, random primers for the preparation of CYP3A4 cDNA probe, Northern hybridization CYP3A4 gene expression differences in the above three groups. Results: The CYP3A4 protein level, activity and mRNA expression in patients with posthepatitic cirrhosis were significantly lower than those in normal liver (P <0.01), but there was no significant difference between the patients with obstructive jaundice and the normal liver. CONCLUSIONS: The expression of CYP3A4 mRNA in cirrhotic patients is significantly decreased, resulting in the decrease of isoenzyme content and enzyme activity. The hepatic metabolism of many drugs, including intravenous anesthetics, is decreased, suggesting that alteration of drug enzymes should be considered in clinical anesthesia, Patient’s anesthetic dose.