Department of Surgery, University of Heidelberg, Heidelberg, Germany.
Pancreatology. 2010;10(5):603-12. doi: 10.1159/000288707. Epub 2010 Oct 29.
The mechanism of alcoholic pancreatitis is still unknown. It is of special interest why only about 5% of all alcoholics develop an episode of pancreatitis. We evaluated the role of long-term alcohol intake in the pathogenesis of alcoholic pancreatitis in rats.
To evaluate the effect of long-term alcohol intake, rats were fed either a Lieber-DeCarli control diet (CD) or a Lieber-DeCarli alcohol diet (AD) for 6 weeks. Then, rats were infused over 2 h with either Ringer's solution (CO) or ethanol (E). In additional animals, alcoholic pancreatitis was induced by ethanol combined with hyperlipidemia and temporary pancreatic duct obstruction (EFO). Controls received Ringer's solution combined with hyperlipidemia and temporary pancreatic duct obstruction (RFO). Intravital microscopy (pancreatic perfusion and leukocyte adhesion), alcohol concentrations, amylase, lipase, cholesterine and triglyceride levels in plasma, myeloperoxidase activity and histology were evaluated at different time intervals.
In those animals which received the Lieber-DeCarli control diet, capillary perfusion was reduced in the E group and further reduced in the EFO group as compared to the controls (CO, RFO; p < 0.01). Leukocyte adhesion was significantly increased in rats receiving E (p < 0.01), and was further increased in the combination group EFO (p < 0.01). EFO induced histologically evident acute pancreatitis. The additional administration of a long-term alcohol diet further increased microcirculatory disturbances and pancreatic injury significantly (EFO-AD > EFO-CD).
This study shows that alcoholic pancreatitis is induced by the combination of ethanol and individual cofactors. Chronic alcohol abuse intensifies these changes. Therefore, long-term alcohol intake seems to be a major factor in the pathogenesis of alcoholic pancreatitis.
酒精性胰腺炎的发病机制尚不清楚。特别有趣的是，为什么只有约 5%的酗酒者会发生胰腺炎发作。我们评估了长期饮酒在大鼠酒精性胰腺炎发病机制中的作用。
为了评估长期饮酒的影响，大鼠分别用 Lieber-DeCarli 对照饮食（CD）或 Lieber-DeCarli 酒精饮食（AD）喂养 6 周。然后，用林格氏液（CO）或乙醇（E）对大鼠进行 2 小时输注。在其他动物中，通过乙醇联合高脂血症和暂时性胰管阻塞（EFO）诱导酒精性胰腺炎。对照组接受林格氏液联合高脂血症和暂时性胰管阻塞（RFO）。在不同时间间隔评估胰腺灌流和白细胞黏附的活体显微镜检查、血浆中酒精浓度、淀粉酶、脂肪酶、胆固醇和甘油三酯水平、髓过氧化物酶活性和组织学。
在接受 Lieber-DeCarli 对照饮食的动物中，与对照组（CO、RFO）相比，E 组的毛细血管灌注减少，EFO 组的毛细血管灌注进一步减少（p<0.01）。接受 E 治疗的大鼠白细胞黏附明显增加（p<0.01），在联合组 EFO 中进一步增加（p<0.01）。EFO 诱导了明显的急性胰腺炎组织学变化。长期酒精饮食的额外给药进一步显著增加了微循环障碍和胰腺损伤（EFO-AD>EFO-CD）。
本研究表明，酒精性胰腺炎是由乙醇和个体协同因子的组合引起的。慢性酒精滥用加剧了这些变化。因此，长期饮酒似乎是酒精性胰腺炎发病机制的主要因素。
