Acute pancreatitis (AP) is a clinical entity that is believed to have intracellular activation of digestive enzymes and autodigestion of the pancreas as its central pathophysiologic cause. The noninfectious destruction of pancreatic parenchyma quickly induces an inflammatory reaction at the site of injury. Histologically, AP is characterized by interstitial edema, vacuolization, inflammation and acinar cell necrosis. The diagnosis of AP is based on pancreatic edema index (pancreas weight/body weight) and pancreatic serum enzymes (pancreatic amylase, lipase, immunoreactive trypsin or elastase.
1,2)The induction of the heat shock response enhances the ability of the cells to overcome the effects of the stress.3) The heat shock proteins (HSPs) are involved in the synthesis, degradation, folding, transport, and translocation of proteins. 4,5) HSPs have been classified into six families according to their molecular mass. It is well known that the increased expression of HSPs have protective effects against caerulein-induced pancreatitis in rats or against choline-deficient ethionine-supplemented diet pancreatitis model. [6][7][8] Others reported that the pre-induction of HSP expression has a protective effect against caerulein-induced pancreatitis in mice. Many diseases result in increased levels of HSPs. But caerulein or CCK-induced pancreatitis reduces the levels of pancreatic HSPs. 9,10) Cytokines are important immunoregulatory mediators. Their contribution to the pathogenesis of acute and chronic gastroenterological disorders is obvious. Increased expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF)-a can be detected in inflammatory bowel disease. Pro-inflammatory cytokines such as IL-1, TNF-a, and IL-6 are elevated during AP and are considered to be involved in the pathogenesis of pancreatitis-associated multiple organ dysfunction.11) Elevated serum levels of these cytokines have been demonstrated clinically as well as experimentally in different animal models of AP.
12)Among the neurohormonal regulators, Cholecystokinin (CCK) is a well known gastrointestinal hormone and neural agonist to induce the release of pancreatic digestive enzymes 13) . At supramaximal doses (doses greater than those that cause maximal secretion of digestive enzymes by the pancreatic acinar cell), CCK is able to cause pancreatic responses. 14,15) Statins, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are the most potent lipidlowering agents currently available, and are being prescribed in the treatment of hyperlipidemia. 16,17) Statins are also effective for the reduction of vascular inflammation. Thus, we set out to investigate the effects of statin as anti-inflammatory agent on AP.
MATERIALS AND METHODSReagents Avidin-peroxidase and 2Ј-AZINO-bis (3-ethylbenzithiazoline-6-sulfonic acid) tablets substrate and CCK-8 were purchased from Sigma (St. Louis, MO, U.S.A.). Anti-HSP60 antibodies were purchased from Stressgen (British Columbia, Canada). Anti-rat IL-6, TNF-a and IL-1b ant...
