| Background:Acute pancreatitis(AP) is a common disease with great variability in severity. The mortality rate for severe acute pancreatitis(SAP) is about 10～30%,whereas that for mild acute pancreatitis(MAP) is about 2.3%. The main causes of death include circulatory shock, cardiac insufficiency, renal, and respiratory and hepatic failure, indicating that systemic inflammation response syndrome (SIRS) and multiple organ failure (MOF) occurred. Thus,the prognosis of SAP is highly dependent on prevention and on appropriate measures to prevent SIRS or MOF happened. Our understanding of the pathophysiology of AP has evolved dramatically in recent years. Factors involved in this progression include activated white blood cells, soluble cytokine and chemokine mediators, and the interaction of these cellular protein components with vascular endothelium. It is now apparent that enzyme induced,macrophage-derived, extrapancreatic production of cytokines mediates distant organ injury.Although the detrimental effects of proinflammatory cytokines,such as TNF-αor interleukin-1β(IL-1β) on organ function during AP are well documented,inhibition of TNF-αor IL-1 did not abolish pancreatitis-associated SIRS and MOF in laboratory animals or clinical trial, suggesting that other pathways of organ injury are functional. The effective inhibition and regulation of the pivotal pathways and controlling the production of cytokines will reduce the severity of the SIRS and MOF. There have not many signal transduction pathways which regulate the production of the cytokines. There has been evidence that the mitogen-activated protein kinases (MAPKs) are the one of key regulators of proinflammatory cytokines gene expression. MAPKs belong to the most ancient signaling molecules and control a vast array of physiologic processes. MAPKs are mainly located in the cytoplasm in resting state and enter the nucleus after activation.They compose a family of highly conserved proteins in multicellular organisms.The MAPK signaling pathway typically consists of three hierarchical protein kinases which include:MAPK kinase kinase (MAPKKK), MAPK kinase(MAPKK), and MAPK. MAPKKK phosphorylates and activates MAPKK, which, in turn phosphorylates and activates MAPK. Activated MAPK modulates the activity of a number of downstream transcription factors and protein kinases by phosphorylation, thereby controlling gene expression and cell behavior(mitosis, cytokinesis, metabolism, and cell death). Four major mammalian MAPK families have been identified: the extracellular signal-regulated kinases 1 and 2(ERK1/2), c-Jun N-terminal kinase(JNK), p38 kinase and big mitogen-activated protein 1( BMKl). Recently, It have been reported that JNK,ERK1/2 or p38MAPK activity in the pancreas was already increased at early time points in vivo and vitro on cerulein-induced animal pancreatitis models. Blocking the effect of the MAPKs phosphorylation with MAPKs special inhibitors can reduce the production of cytokines and improve the survival rate of the animals. To date there is ample evidence of successful administration and efficacy of MAPKs inhibitor on MAP, howere,little is known about the role of MAPKs in the pathogenesis of experimental SAP and only a few studies have investigated the therapeutic effects of MAPKs inhibitor in the course of local tissue destruction and SIRS in experimental SAP.The pathophysiological mechanisms responsible for pancreatic inflammation and ultimate organ injury are not thoroughly elucidated, and there are few of any effective treatments. A better understanding of the molecular players involved in the series of events leading to pancreatic inflammation could eventually lead to novel preventive and therapeutic strategies.Therefore, the study on the role of MAPKs signal transduction pathway in the pathogenesis of SAP may supply a new approach for future basic studies and clinical therapy of SAP. In this study, we investigated the role of MAPKs and effect of blocking the MAPK was also studied. Objective:To study the dynamic...
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