Foitzik T, Lewandrowski K B, Fernández-del Castillo C, Rattner D W, Klar E, Warshaw A L
Department of Surgery, Massachusetts General Hospital, Boston.
Arch Surg. 1994 Oct;129(10):1081-5. doi: 10.1001/archsurg.1994.01420340095018.
To evaluate the factors thought to be involved in the pathogenesis of acute pancreatitis associated with alcohol.
The mechanism of alcohol-induced pancreatitis is believed to involve synergistic effects of various pathogenetic factors. The present study was designed to evaluate the possible contribution of pancreatic duct obstruction, physiologic exocrine stimulation, or secretory hyperstimulation to alcohol-induced pancreatic injury.
Wistar rats were allocated randomly to a control group (group 1), or to a group with pancreatic duct obstruction (group 2), physiologic exocrine stimulation (group 3), ductal obstruction and exocrine stimulation (group 4), or exocrine hyperstimulation with the cholecystokinin analogue cerulein (group 5). Three hours after this pretreatment, animals in each experimental group were randomly divided into two subgroups for intragastric administration of either water (groups 1A through 5A) or beer (groups 1B through 5B). Test solutions were instilled over 9 hours (total amount of alcohol administered, 4.8 g/kg). Twenty-four hours after beginning the test infusion, animals were killed for histologic evaluation of pancreatic edema and determination of an acinar cell necrosis score. Serum amylase levels were determined at 3, 9, and 24 hours.
No increase in amylase levels or significant morphologic changes were found in control animals (group 1A) or in animals subjected to physiologic exocrine stimulation (group 2A). Pancreatic duct obstruction, with or without physiologic exocrine hyperstimulation (groups 3A and 4A), and exocrine hyperstimulation (group 5A) induced pancreatitis of similar severity with minor acinar cell damage. Alcohol superimposed on exocrine hyperstimulation (group 5B) increased acinar cell injury (group 5A, 0.4 +/- 0.1 points vs 5B, 1.0 +/- 0.2 points; P < .05) and serum amylase levels at 24 hours (group 5a, 41 +/- 6 U/L vs group 5B, 72 +/- 11 U/L; P < .05), whereas no differences between subgroups A and B (water vs beer) were found in groups 1 through 4.
Our findings suggest that the pathogenesis of acute alcoholic pancreatitis may require a state of exocrine hyperstimulation, perhaps via cholecystokinin, but do not support a role for constriction or obstruction of Oddi's sphincter.
评估被认为与酒精性急性胰腺炎发病机制相关的因素。
酒精性胰腺炎的发病机制被认为涉及多种致病因素的协同作用。本研究旨在评估胰管梗阻、生理性外分泌刺激或分泌过度刺激对酒精性胰腺损伤可能产生的影响。
将Wistar大鼠随机分为对照组（第1组），或胰管梗阻组（第2组）、生理性外分泌刺激组（第3组）、导管梗阻与外分泌刺激组（第4组）、或用胆囊收缩素类似物蛙皮素进行外分泌过度刺激组（第5组）。在这种预处理3小时后，每个实验组的动物随机分为两个亚组，分别经胃给予水（第1A至5A组）或啤酒（第1B至5B组）。测试溶液在9小时内滴注（给予的酒精总量为4.8 g/kg）。在开始测试输注24小时后，处死动物以进行胰腺水肿的组织学评估并确定腺泡细胞坏死评分。在3、9和24小时测定血清淀粉酶水平。
在对照动物（第1A组）或接受生理性外分泌刺激的动物（第2A组）中未发现淀粉酶水平升高或明显的形态学变化。伴有或不伴有生理性外分泌过度刺激的胰管梗阻（第3A和4A组）以及外分泌过度刺激（第5A组）诱导了严重程度相似且腺泡细胞损伤较小的胰腺炎。外分泌过度刺激叠加酒精（第5B组）增加了腺泡细胞损伤（第5A组，0.4±0.1分 vs 第5B组，1.0±0.2分；P<.05）以及24小时时的血清淀粉酶水平（第5A组，41±6 U/L vs 第5B组，72±11 U/L；P<.05），而在第1至4组中A、B亚组（水与啤酒）之间未发现差异。
我们的研究结果表明，急性酒精性胰腺炎的发病机制可能需要外分泌过度刺激状态，可能是通过胆囊收缩素，但不支持奥迪括约肌收缩或梗阻起作用。
