Matrix Metalloproteinase 9 Aggravates Inflammation And Necrosis Of Experimental Pancreatitis

Objective: To investigate the changes of matrix metalloproteinase-9(MMP-9)in acute pancreatitis and to define the roll of MMP-9 in inflammation and necrosis.Methods: AP was induced in Balb/c mice by intraperioreal injection of caerulein(100mg/kg),MMP inhibitor BB-94(40mg/kg/d)was administered by intraperitoreal injection half hour before AP induction.MMP-9 expression was assessed by reverse transcriptase(RT)-PCR,Western Blot analyse and Enzyme-Linked Immunosorbent Assay(ELISA).Injury of pancreas was determinded by measuring amylase and lipase activities in the serum and histological granding.Inflammation was estimated by measuring IL-1β,IL-6,TNF-α,NF-κB,pNF-κB,IκBα,pIκBα、 expression.The effect of MMP-9 on necrosis was examined,receptor-interacting protein 3(RIP3),mixed lineage kinase domain-like protein(MLKL)and phosphorylation mixed lineage kinase domain-like protein(pMLKL)expression were assessed by Western Blot analysis.Results: MMP-9 mRNA and protein and were markedly upregulated during caerulein-induced AP,MMP-9 in serum was increased in caeruleininduced mice AP and the patients with galle severe acute pancreatitis(GSAP).BB-94 could protect against caerulein-induced pancreatic histopathological damage,reduced plasma amylase and lipase level,and reduced the protein expression of IL-6,TNF-α,pNF-κB,pIκBα;BB-94 induced RIP3 and pMLKL expression.Conclusions: The data suggest that MMP-9 may aggravates inflammation and necrosis of experimental pancreatitis.