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目的 :观察在采用Kupffer细胞选择性阻断剂 -GdCl3 封闭小鼠肝Kupffer细胞活性后 ,奥美拉唑在小鼠体内的代谢动力学变化 ,以进一步探讨Kupffer细胞对药物代谢的影响。 方法 :雄性昆明种小鼠一次性给予GdCl3 (ip ,2 0mg·kg-1) ,于阻断后 6d ,碳粒廓清法测定小鼠的吞噬功能 ;免疫组化法观察CD68在肝脏中的表达 ;取血清测定ALT活性 ,尿素氮及肌酐含量 ,观察Kupffer细胞阻断对肝、肾功能的影响。另取同样处理的小鼠 ,给予奥美拉唑 (iv ,10mg·kg-1) ,分别于给药后 5 ,15 ,30min和 1,2 ,4 ,6 ,8,12 ,2 4h眼眶采血 ,高效液相色谱法测定血药浓度 ,3P87软件计算药代动力学参数。结果 :ipGdCl3 后 ,能明显阻断Kupffer细胞活性 ,肝、肾功能未见受损。奥美拉唑在小鼠体内药动学符合一房室模型。与正常鼠相比 ,奥美拉唑在Kupffer细胞活性阻断的小鼠体内的消除受到明显抑制。K ,CL分别下降 18.7% ,2 .9% ,t1/2 延长 18%。结论 :阻断Kupf fer细胞活性可明显改变奥美拉唑在小鼠体内的代谢与处置 ,提示Kupffer细胞在药物代谢中的作用 ,其机制有待进一步阐明
OBJECTIVE: To observe the pharmacokinetics of omeprazole in mice after Kupffer cell-selective blocker-GdCl3-blocked mouse liver Kupffer cell activity, in order to further explore the effect of Kupffer cells on drug metabolism. METHODS: Male Kunming mice were treated with GdCl3 (ip, 20 mg · kg-1) once a day for 6 days. The phagocytosis of mice was determined by carbon clearance method. The expression of CD68 in the liver was observed by immunohistochemistry Serum ALT activity, urea nitrogen and creatinine were measured to observe the influence of Kupffer cell block on liver and renal function. The same treated mice were also given omeprazole (iv, 10 mg · kg -1) respectively for 5, 15, 30 min and 1, 2, 4, 6, 8, 12, , HPLC determination of plasma concentration, 3P87 software to calculate pharmacokinetic parameters. Results: After ipGdCl3, the activity of Kupffer cells was obviously blocked, and the liver and kidney functions were not damaged. Omeprazole in mice pharmacokinetics consistent with a one-compartment model. Omeprazole was significantly suppressed in mice with Kupffer cell-activity block compared to normal mice. K, CL decreased by 18.7%, 2.9%, t1 / 2 by 18%. Conclusion: Blocking the activity of Kupf fer can significantly change the metabolism and disposal of omeprazole in mice, suggesting that the mechanism of Kupffer cells in drug metabolism needs to be further elucidated