Yuasa C, Irimura K, Oka T
Pharmacology Research Laboratory, R&D Headquarters Tokushima Research Center, Taiho Pharmaceutical Co., LTD., Japan.
J Pharmacol Toxicol Methods. 1998 Jun;39(4):221-8. doi: 10.1016/s1056-8719(98)00026-4.
Alcohol consumption causes acute alcohol pancreatitis and worsens the prognosis; however, there is no useful model for elucidation of the mechanism underlying this worsening. The aim of our study was to establish a new prognostic model of acute alcohol pancreatitis in rats. To ascertain the effect of continuous infusion of ethanol on each phase, i.e., progression and recovery, in caerulein-induced pancreatic injury in rats, we infused a physiological or supramaximal dose of caerulein intravenously to conscious Wistar rats for up to 6 h (time: 0-6 h) with or without ethanol infusion for 9 h (time: 3-12 h). Ethanol did not induce the pancreatic injury alone or when combined with a physiological dose of caerulein. In the progression phase, ethanol infusion for 3 h (time: 6 h) did not aggravate the pancreatic injury induced by a supramaximal dose of caerulein in terms of plasma amylase and lipase activities but did increase the pancreatic calcium level. In the recovery phase, however, ethanol infusion for 9 h (time: 12 h) significantly restrained the recovery from pancreatic injury as monitored in terms of these activities. Further, ethanol infusion for 9 h significantly increased the cumulative urinary excretion of amylase from 12 to 27 h but did not do the same from 0 to 12 h. In the histological evaluation at 27 h, the induction of acinar cell vacuolization and dilation of the glandular lumina and ducts were significant in the caerulein plus ethanol-treated group. Our findings suggest that ethanol administration delays the recovery rather than worsens the progression in acute pancreatic injury induced by exocrine hyperstimulation, and we consider our experimental model to be a useful tool for studying the pathogenesis of worsening prognosis in acute alcohol pancreatitis.
饮酒会引发急性酒精性胰腺炎并使预后恶化；然而，目前尚无用于阐明这种恶化潜在机制的有效模型。我们研究的目的是建立一种大鼠急性酒精性胰腺炎的新预后模型。为确定持续输注乙醇对大鼠蛙皮素诱导的胰腺损伤各阶段（即进展期和恢复期）的影响，我们对清醒的Wistar大鼠静脉注射生理剂量或超最大剂量的蛙皮素，持续6小时（时间：0 - 6小时），同时在3 - 12小时内给予或不给予乙醇输注9小时。单独使用乙醇或乙醇与生理剂量的蛙皮素联合使用均未诱导胰腺损伤。在进展期，就血浆淀粉酶和脂肪酶活性而言，输注3小时乙醇（时间：6小时）并未加重超最大剂量蛙皮素诱导的胰腺损伤，但确实增加了胰腺钙水平。然而，在恢复期，就这些活性监测而言，输注9小时乙醇（时间：12小时）显著抑制了胰腺损伤的恢复。此外，输注9小时乙醇显著增加了12至27小时淀粉酶的累积尿排泄量，但在0至12小时并未如此。在27小时的组织学评估中，蛙皮素加乙醇处理组腺泡细胞空泡化以及腺管和导管扩张的诱导显著。我们的研究结果表明，乙醇给药会延迟外分泌过度刺激诱导的急性胰腺损伤的恢复，而非加重其进展，并且我们认为我们的实验模型是研究急性酒精性胰腺炎预后恶化发病机制的有用工具。
