A Pathological Study Of The Role Of COX-2 In Rat Liver Damage Induced By Severe Acute Pancreatitis

[Background] About 15% to 20% patients with accurate pancreatitis (AP) present with a sever form, severe acute pancreatitis (SAP). Those patients usually have severe symptoms and complications, and high mortality. Multiple organ failure (MOF) is frequent in the early phase of disease. Liver is the earliest organ that is damaged besides pancreas during SAP, and the mortality will reach up to 50% when MOF occurs. The mechanism how MOF develops during SAP is still unclear, which explains the unsatisfactory treatment and high mortality of this condition. Liver injury is a common complication of SAP. The damage appears early and develops quickly. Both morphological and functional changes of liver are remarkable. Although the mechanisms of liver damage in SAP are not totally unfolded, existing studies demonstrated that the following factors have been involved: the toxic factors released by pancreas, cytokines and inflammatory mediators with tumor necrosis factor-alpha (TNF-α) being a key factor, and anatomic factors. Multiple inflammatory mediators and cytokines are involved in liver injury. Prostaglandin (PE) is one of the important inflammatory mediators that plays a central role in the cytokine network. Among the candidate factors in the initial stage of inflammation, cyclooxygenase-2 (Cox-2) is a key enzyme for prostaglandin synthesis, which could induce apoptosis, pathological changes and liver damage. During liver damage, hormones, cytokines, endotoxin and the metabolic products of the oxidative could induce the expression of cox-2. The roles of Cox-2 in SAP-induced liver injury, and the effect of cox-2 on hepatic metabolisms as well as on the cellular and morphological changes of liver, have been well studied. In multiple factor-induced liver injury, cytokines, endotoxin and the products of oxidative stress induce the expression of cox-2 and synthesis of PGs that further accelerate liver damage. Although the incidence of liver failure is less than lung and kidney failure, liver is the earliest organ damaged during SAP-induced MOF. Moreover, due to its importance in regulating the physiological functions and maintaining body homeostasis, liver...