苯巴比妥诱导下大鼠肝微粒体药酶活性与膜流动性变化的相关性

本文用ANS和DPH为荧光探剂,研究苯巴比妥(PB)诱导下大鼠肝微粒体膜脂区流动性与膜药酶活性变化的相关性。结果表明,经PB诱导后在增加肝微粒体蛋白质含量,P-450含量及NADPH-细胞色素C还原酶等酶活性的同时,肝微粒体膜流动性明显增大,且膜深层流动性的增大与膜氨基比林N-脱甲基酶、细胞色素C还原酶活性增加有明显的直线正相关。膜胆固醇/碑脂比值明显降低。此结果提示,肝微粒体膜流动性的适当增大与PB增加单胺氧化酶系统活性之间可能存在着某种联系。

STUDIES ON CORRELATION BETWEEN LIVER DRUG METABOLIZING ENZYME ACTIVITIES AND MICROSOMAL MEMBRANE FLUIDITY IN PHENOBARBITAL TREATED RATS

By the use of ANS(1 - anilinonaphthalene- 8 - sulfonate) and DPH( 1,6- diphenyl-1, 3, 5-hexatriene)as fluorescent probes, correlation between liver microsomal membrane fluidity and drug metabolizing enzyme activity has been studied in rats. phenobarbital(PB) ip treatment caused an increase in P - 450 content, cytochrome C reductase.amiropyrine N - demethylase(AM D)and glutathione S - transferase(GST)activities by 78, 66,270 and 52%, respectively. However, there was a simultaneous decrease in microsomal membrane fluorescent intensity and microviscosity, i. e. an increase in membrane fluidity. There is a positive linear correlation between microsomal membrane fluidity and cytochrome C reductase and AMD activities (r= 0. 798, r= 0. 781, respectively, P<0.05). This result suggests that there may be some relationship between microsomal membrane fluidity and drug- metabolizing enzymatic activities in PB - treated rats.