Carmichael F J, Orrego H, Saldivia V, Israel Y
Department of Anesthesia, University of Toronto, Ontario, Canada.
Hepatology. 1993 Aug;18(2):415-21.
It has been postulated that the beneficial effects of the antithyroid drug propylthiouracil in the treatment of alcoholic liver disease depend primarily on the action of propylthiouracil in suppressing the increase in hepatic oxygen consumption induced by ethanol. The evidence for this effect of propylthiouracil is derived from studies in which liver oxygen consumption has been determined in in vitro preparations. In our study the effects of ethanol and propylthiouracil on liver oxygen consumption were assessed in vivo in an unrestrained and unanesthetized rat model, where liver blood flow and hepatic vein and portal vein oxygen content can be measured. Data show that the liver oxygen consumption increased in rats treated with ethanol-containing liquid diets for 4 to 6 wk, both on withdrawal of alcohol (30%, p < 0.01), and after readministration of ethanol (50%, p < 0.01). Single-dose ethanol administration increased portal tributary blood flow without affecting hepatic arterial blood flow in both controls and rats withdrawn from long-term ethanol treatment. Long-term ethanol administration per se had no effect on portal tributary blood flow; however, hepatic arterial blood flow was increased by 38% (p < 0.01). Treatment with propylthiouracil for 5 days resulted in complete suppression of the increase in liver oxygen consumption induced by long-term ethanol administration. Propylthiouracil treatment also attenuated the increase in portal tributary blood flow after the administration of a single dose of ethanol. These determinations were made 24 hr after the last dose of propylthiouracil.(ABSTRACT TRUNCATED AT 250 WORDS)
据推测，抗甲状腺药物丙硫氧嘧啶在治疗酒精性肝病中的有益作用主要取决于丙硫氧嘧啶抑制乙醇诱导的肝脏氧消耗增加的作用。丙硫氧嘧啶这种作用的证据来自于在体外制剂中测定肝脏氧消耗的研究。在我们的研究中，在未受限制且未麻醉的大鼠模型中体内评估了乙醇和丙硫氧嘧啶对肝脏氧消耗的影响，在该模型中可以测量肝脏血流量以及肝静脉和门静脉的氧含量。数据显示，用含乙醇的液体饲料喂养4至6周的大鼠，在戒酒时（增加30%，p<0.01）以及再次给予乙醇后（增加50%，p<0.01），肝脏氧消耗均增加。单剂量给予乙醇可增加门静脉支流血流量，而对对照组和长期乙醇处理后戒断的大鼠的肝动脉血流量均无影响。长期给予乙醇本身对门静脉支流血流量无影响；然而，肝动脉血流量增加了38%（p<0.01）。用丙硫氧嘧啶治疗5天可完全抑制长期给予乙醇诱导的肝脏氧消耗增加。丙硫氧嘧啶治疗还减弱了单剂量给予乙醇后门静脉支流血流量的增加。这些测定在最后一剂丙硫氧嘧啶给药24小时后进行。（摘要截短至250字）
