Braganza J M
University Department of Medicine The Royal Infirmary, Manchester, UK.
Digestion. 1998;59 Suppl 4:1-12. doi: 10.1159/000051438.
The traditional ductal model for the development of chronic pancreatitis leaves many questions unanswered and it has not facilitated management. An alternate philosophy centres on the acinar cell as the site of mounting oxidant stress, usually as a result of steady exposure to xenobiotics that induce cytochrome P450 mono-oxygenases while depleting glutathione: ductal changes are regarded as secondary, disease-compounding manifestations of the oxidant environment. Within this framework each burst of oxidant stress jeopardises exocytosis, to trigger an attack of pancreatitis by interfering with the methionine-to-glutathione transsulphuration pathway, which interacts closely with ascorbate and selenium. The resulting diversion of free radical oxidation products into the pancreatic interstitium causes mast cells to degranulate, thereby provoking inflammation, the activation of nociceptive axon reflexes, and profibrotic interactions.
传统的慢性胰腺炎发展的导管模型留下了许多未解答的问题，并且它并未促进治疗。另一种理念则以腺泡细胞为产生氧化应激的部位为核心，这通常是由于持续接触诱导细胞色素P450单加氧酶同时消耗谷胱甘肽的外源性物质所致：导管变化被视为氧化环境的继发性、疾病加重表现。在这个框架内，每次氧化应激爆发都会危及胞吐作用，通过干扰与抗坏血酸和硒密切相互作用的蛋氨酸-谷胱甘肽转硫途径引发胰腺炎发作。由此产生的自由基氧化产物转移到胰腺间质中会导致肥大细胞脱颗粒，从而引发炎症、伤害性轴突反射的激活以及促纤维化相互作用。
