Park G R, Miller E
Anaesthesia Drug Metabolism Laboratory, Addenbrooke's Hospital, Cambridge.
Anaesthesia. 1996 May;51(5):431-4. doi: 10.1111/j.1365-2044.1996.tb07785.x.
Liver samples were obtained at hepatectomy from patients with end stage alcoholic liver disease (n = 5), primary biliary cirrhosis (n = 5) and chronic rejection needing retransplantation (n = 5). Normal liver material was also obtained from five organ donors. From these samples microsomes were made containing cytochrome P450 3A. The amount of this enzyme was measured by Western immunoblotting and its function assessed by measuring the rate of production of two metabolites of midazolam, 1-hydroxy midazolam and 4-hydroxy midazolam. There was a wide range in all groups for both the expression and function of this enzyme. Liver tissue affected by cirrhotic disease showed greater preservation of enzyme function than that affected by hepatocellular disease. There was a good correlation between the expression of the enzyme and production of the 1-hydroxy metabolite, but a poor correlation between production of the 4-hydroxy metabolite and expression. This poor correlation may reflect the failure to measure the specific enzyme responsible for producing 4-hydroxy midazolam.
在肝切除术中从患有终末期酒精性肝病（n = 5）、原发性胆汁性肝硬化（n = 5）和需要再次移植的慢性排斥反应（n = 5）的患者身上获取肝脏样本。还从五名器官供体获取了正常肝脏组织。从这些样本中制备了含有细胞色素P450 3A的微粒体。通过蛋白质免疫印迹法测量该酶的量，并通过测量咪达唑仑的两种代谢产物1-羟基咪达唑仑和4-羟基咪达唑仑的生成速率来评估其功能。在所有组中，该酶的表达和功能都有很大差异。受肝硬化疾病影响的肝组织比受肝细胞疾病影响的肝组织显示出更好的酶功能保留。该酶的表达与1-羟基代谢产物的生成之间存在良好的相关性，但4-羟基代谢产物的生成与表达之间的相关性较差。这种较差的相关性可能反映了未能测量负责生成4-羟基咪达唑仑的特定酶。
