Yang W, Benjamin I S, Sherwood R, Alexander B
Academic Department of Surgery, Guy's King's & St Thomas' School of Medicine, St Thomas' Hospital, London, United Kingdom.
J Pharmacol Toxicol Methods. 1998 Nov;40(4):227-34. doi: 10.1016/s1056-8719(99)00010-6.
Twelve male Wistar rats were anaesthetized with pentobarbitone (3 mg 100g(-1) i.p.), the livers were excised and perfused in vitro through the hepatic artery and portal vein at constant flow rates of 0.32+/-0.01 (mean+/-S.E.) and 0.98+/-0.03 ml min(-1) g liver(-1), respectively. The tone of the preparation was raised by methoxamine (7.5 x 10(-6) M). Responses to mid-range doses of acetylcholine (-11 log mol) and sodium nitroprusside (-9 log mol) produced submaximal degrees of vasodilatation (-log mol ED50 = 12.18+/-0.08) and (-log mol ED50 = 9.95+/-0.23), respectively, which did not subside until 5.5 h of perfusion. These did not coincide with the increase in activities of lactic acid dehydrogenase (LDH) and aspartate serine transaminase (AST) activity at 2.5 h, which were indicative of hepatocellular mitochondrial and cytoplasmic damage, respectively. Vascular responses suggested that there was little deterioration in endothelial or smooth muscle function in the hepatic artery up to 5 h perfusion. This model can be reliably used to investigate endothelium-dependent and -independent vasodilators in vascular pharmacological studies of the rat liver although some minimal increases may occur in AST and LDH activity before hemodynamic changes appear at 5.5 h.
选用12只雄性Wistar大鼠，用戊巴比妥（3 mg·100g⁻¹，腹腔注射）麻醉，切除肝脏后在体外通过肝动脉和门静脉进行灌注，流速分别恒定为0.32±0.01（均值±标准误）和0.98±0.03 ml·min⁻¹·g肝脏⁻¹。用甲氧明（7.5×10⁻⁶ M）提高标本的张力。对中等剂量乙酰胆碱（-11 log mol）和硝普钠（-9 log mol）的反应分别产生次最大程度的血管舒张（-log mol ED50 = 12.18±0.08）和（-log mol ED50 = 9.95±0.23），这种舒张在灌注5.5小时后才消退。这些反应与2.5小时时乳酸脱氢酶（LDH）和天冬氨酸丝氨酸转氨酶（AST）活性的增加不一致，这两种酶活性的增加分别指示肝细胞线粒体和细胞质损伤。血管反应表明，在灌注长达5小时时，肝动脉内皮或平滑肌功能几乎没有恶化。该模型可可靠地用于大鼠肝脏血管药理学研究中内皮依赖性和非内皮依赖性血管舒张剂的研究，尽管在5.5小时出现血流动力学变化之前，AST和LDH活性可能会有一些微小的增加。
