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虽然已有大量的人肾素抑制剂被研究开发,但它们的代谢作用广泛,通过胆囊排出迅速,而且口服吸收不完全,因此生物利用度仍有一定的局限性。由于缺乏合适的动物模型进行评价,使化学结构改造及剂型的确定均存在一定的困难。本文介绍了一个静脉滴注入肾素以快速鉴定肾素抑制剂的大鼠模型,与滴注猪肾素模型相比,该模型与体外动力学研究结果一致,可用于新的体内有效的肾素抑制剂的筛选和药效动力学的研究。雄性SD大鼠.体重200g左右,禁食24h后,麻醉双侧肾切除,以刺激血浆血管紧张素原浓度的升高。18h后,再次麻醉,气管插管,切断双侧迷走神经;颈动脉插管记录血压;插入胃管用于灌胃给药;颈静脉注射3-甲氨基
Although a large number of human renin inhibitors have been researched and developed, their metabolic effects are extensive, they are excreted rapidly through the gallbladder, and their oral absorption is incomplete. Therefore, bioavailability still has some limitations. Due to the lack of suitable animal models for evaluation, there are some difficulties in the reformation of chemical structures and the determination of dosage forms. This article presents a rat model of intravenous infusion of renin to rapidly identify renin inhibitors. This model is consistent with in vitro kinetic studies and may be used in new in vivo-effective kidneys compared with instillation of porcine renin Screening of Inhibitors and Pharmacodynamic Studies. Male SD rats weighing about 200 g, fasted for 24 h after anesthesia bilateral nephrectomy to stimulate the plasma concentration of angiotensinogen. 18h later, re-anesthesia, tracheal intubation, bilateral vagus nerve cut off; carotid artery catheterization of blood pressure; inserted into the stomach for intragastric administration; jugular vein injection of 3-methylamino