First Department of Medicine, University of Szeged, Szeged, Hungary.
Gut. 2011 Apr;60(4):544-52. doi: 10.1136/gut.2010.218461. Epub 2010 Sep 28.
There is an unacceptably high mortality in acute pancreatitis, which is due to the lack of specific treatments for the disease. A major reason stated to account for the inability to develop effective treatments is that there are multiple pathobiologic pathways activated in the acinar cell mediating pancreatitis making it difficult to choose molecular targets for therapeutic strategies. However, this reasoning limits opportunities for therapeutic development because it does include another important participant in pancreatitis - the pancreatic duct cells. The most recent advance in pancreatitis research is that depletion of both glycolytic and oxidative ATP synthesis is a common event in both acinar and ductal cells. Although ATP has a very short half-life in the blood and is hydrolysed to ADP, there is clear evidence that encapsulating ATP into liposomes can effectively drive ATP into the cells which can be effective in protecting them from necrosis. In this review, we will examine the effects of different insults associated with pancreatitis on both the acinar and ductal components of the exocrine pancreas pointing out the role of the ductal epithelial responses in both attenuating and increasing the severity of pancreatitis. In addition, we propose that exogenous ATP administration may restore ductal and acinar function providing therapeutic benefit.
急性胰腺炎的死亡率高得令人无法接受，这主要是由于缺乏针对该疾病的特定治疗方法。无法开发出有效治疗方法的一个主要原因是，在介导胰腺炎的腺泡细胞中激活了多种病理生物学途径，这使得很难选择用于治疗策略的分子靶点。然而，这种推理限制了治疗开发的机会，因为它没有包括胰腺炎的另一个重要参与者 - 胰腺导管细胞。胰腺炎研究的最新进展是，糖酵解和氧化型 ATP 合成的耗竭是腺泡细胞和导管细胞中的共同事件。尽管 ATP 在血液中的半衰期非常短，并被水解为 ADP，但有明确的证据表明将 ATP 封装到脂质体中可以有效地将 ATP 驱动到细胞中，从而有效地保护它们免受坏死。在这篇综述中，我们将检查与胰腺炎相关的不同损伤对胰腺外分泌腺的腺泡和导管成分的影响，指出导管上皮反应在减轻和增加胰腺炎严重程度中的作用。此外，我们提出外源性 ATP 给药可能恢复导管和腺泡的功能，从而提供治疗益处。
