Experimental Study About The Expressions Of Matrix Metalloproteinase-2 And Tissue Inhibitor Of Metalloproteinase-2 In Acute Pancreatitis

ObjectiveSevere acute pancreatitis (SAP) is a systemic disease, and the mulitisys-tem organ failure ( MSOF) induced by it is associated with a high morbidity and mortality. Animal models of MSOF induced by circulating endotoxin lipopolysa-charide, hypoxia, microembolization, ischemia/reperfusion injury, and hemor-rhagic shock have implicated polymorphonuclear leukocytes ( PMNs) as a cellular mediator of organ injury. A critical step in tissue invasion by PMNs is limited digestion of the basement membrane and of the surrounding extracellular matrix. This process is the result of the imbalance between matrix metalloproteinases ( MMPs) zymogen activations and interaction of the active forms with specific tissue inhibitors of metalloproteinases (TIMPs). In this study, we made a discuss about the expressions of MMP-2 and TIMP-2 in the pancreatic tissues of the mice SAP models and the relationships with the degree of the pancreatic organ injuries.Materials and MethodsSAP was induced by retrograde infusion of 5% Sodium taurocholate into the pancreatic duct. Sham animals underwent a laparotomy without induction of pancreatitis. Sections were stained with hematoxylin and erosin. All specimens were graded for the degree of edema, inflammatory infiltrate, necrosis, and hemorrhage. The stains of MMP-2 and TIMP-2 were completed by immunohistochemi-cal SABC methods.ResultsThe MMP-2 and T1MP-2 were stained in cytoplasms of pancreas cells. The expressions of MMP-2 were significantly lower in cases of Sham group than that of SAP group (P <0.05 ). The expressions of TIMP-2 were significantly lower in cases of SAP group than that of Sham group ( P < 0. 05 ). The expressions of MMP-2 were positively correlated with pathologic severities (P <0.05). The expressions of TIMP-2 were negatively correlated with pathologic severities (P <0. 05).DiscussionsSAP is a potentially lethal disease, which is associated with a high morbidity and mortality. Most attacks of acute pancreatitis are mild and self-limiting. In about 20% of cases, however, SAP occurs, which often results in multiple systemic complications. Leukocytes activation in SAP leads to multiorgan failures and is the most important factor contributing to the death in patients with SAP. Some studies have impicated PMNs as a cellular mediator of organ injury induced by SAP. A critical step in tissue invasion by PMNs is limited digestion of the basement membrane and of the surrounding extracellular matrix.The MMPs are a family of enzymes that share sequence homogies and are involved in a variety of physiological and pathological processes that require extracellular matrix degradation. MMPs are secreted as proenzymes, activated ex-tracellularly by limited proteolysis, and are inhibited by TIMPs.Among these MMPs, the type IV collagenases ( MMP-2 and MMP-9) are particularly important in tissue infiltration by PMNs during inflammation because of the abundance of type IV collagen in the vascular basement membrane. The type IV collagenases or gelatinases degrade a variety of ECM proteins, including type IV and type I collagen, fibronectin, laminin and elastin.The observation that MMPs and TIMPs are central to tissue remodeling and may contribute to organ failure promoted us to investigate the role of MMPs andTIMPs in acute panreatitis. In this study, we found that the expression of MMP-2 in pancreas of SAP mice were elevated, otherwise TIMP-2 were significantly declined. Additionally above two indexes changes were in accord with that of the pathologic severity of the pancreatitis.ConclusionThe increased MMP-2 expression and decreased TIMP-2 expression contribute to the organ injury in SAP. The determinations of above two factors are helpful to the estimation of the development and prognosis of acute pancreastitis.