年龄对大鼠肝脏生物转化功能及膜流动性的影响

通过与青年(3～4月)及中年(14月)组比较,研究了老年(24月)大鼠肝脏生物转化酶活性改变及膜流动性变化。结果表明,老年大鼠肝微粒体P-450含量、NADPH-细胞色素C还原酶活性无明显改变,但氨基比林N-脱甲基酶、苯胺羟化酶活性明显降低,且微粒体及胞浆GST、胞浆GSH-Px活性也明显下降;同时肝微粒体膜脂区流动性明显降低,膜Ch/PL值显著增大。研究提示,微粒体膜脂质环境及流动性变化与上述生物转化功能改变可能有一定的联系。

EFFECT OF AGEING ON HEPATIC BIOTRANSFORMATION FUNCTION AND MICROSOMAL MEMBRANE FLUIDITY IN RATS

Microsomes were isolated from livers of male Sprague-Dawley rats at 3-4, 14 and 24 months of age for each group for the determination of monooxygenase components and drug metabolism activities. Some GSH-related enzyme activities in microsomes and cytosol were also measured. DPH (1,6-diphenyl-1,3,5-hexatriene) was used to determine the microsomal membrane lipid region fluidity. Microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activities remained unchanged in old rats, but there were significantly decreases in cytochrome P-450 dependent aminopyrine N-demethylase and aniline hydroxylase activities. Glutathione S-transferase (GST) in cytosol and microsomes and glutathione peroxidase (GSH-Px) in cytosol were also decreased in old rats. Simultaneously, microsomal membrane fluidity of 24-month old rats decreased (measured at 25 degrees C and 37 degrees C), accompanied by an elevation of cholesterol/phospholipid ratio. Results suggest that there might be some relationship between the lipid environment and membrane fluidity changes and the decreases of hepatic biotransformation function.