适于研究药物相互作用的肝脏灌流模型  

Assessment of an optimized model of rat liver perfusion for hepatic drug-drug interactions

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作  者:印绮平[1] 王宏图[1] 张静华[1] 奚念朱 

机构地区:[1]上海医科大学华山医院临床药学研究室,上海200040 [2]药学研究所生物药剂研究室,上海200032

出  处:《中国临床药学杂志》1999年第1期36-39,共4页Chinese Journal of Clinical Pharmacy

摘  要:目的:改进和建立大鼠离体肝脏灌流模型.方法:采用Krebs-Henseleit 缓冲液(pH7.4)为港灌流液基液,含2%透析48h的牛血清白蛋白组分V、20%(V:V)洗过的人红细胞和0.3%葡萄糖.灌流速度1.5ml·min^(-1)·g^(-1),温度(37±0.5)℃,灌流压力1.7~1.33pKa.测定大鼠灌流过程中胆汁分泌量、耗氧量及灌流液pH、Na^+、K^+水平,并观察肝脏外观变化和组织切片的细胞形态学,评定肝脏功能.结果:本系统灌流中大鼠的各项考察指标正常,离体肝脏的存活力可达3h.结论:该模型适用于研究药物在肝脏代谢中的相互作用及其发生机制,也可用于研究某些药物特殊的代谢动力学特征.AIM: To develop a convenient and effective model of isolated perfused. METHODS:Conditions which influence the viability and integrity of the isolated perfused rat liver (IPRL). Rat livers were perfused with Krebs-Henseleit buffer with 2% bovine serum albumin fraction V, 20% red blood cells and 0. 3% glucose. The perfusion medium was gassed with carbogen and maintained at pH 7. 4 during perfusion procedure. Various physio-logical parameters of the model were investigated. These include: bile flow rate, oxygen consumption of perfused livers, pH of perfusate, Na^+ and K^+ level in perfusate, and the finestructure of hepatocytes. RESULTS: During 3 h perfusion in this system, the rat liver func-tion was normal. The perfused rat liver could be viable for 3 h. CONCLUSION: This model is reliable and suitable for the study of metabolic drug-drug interactions occurring in the rat.

关 键 词:肝脏灌流 药物相互作用 代谢动力学 模型 

分 类 号:R969.2[医药卫生—药理学]

 

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