The Relationships Of Matrix Metalloproteinase-9 And Brain Damage In Rats With Acute Necrotizing Pancreatitis

Objective To investigate pathological changes, variation of MMP-9 in brain and MMP-9, GFAP in serum and to explore the therapeutic effect of methylprednisolone in early stage of acute necrotizing pancreatitis associated brain damage model in rats. At the same time to explain the mechanism of brain damage in acute necrotizing pancreatitis and provide a serum biochemical maker of acute necrotizing pancreatitis associated brain damage for reference of diagnosis and therapy.Methods Male SD rats were divided into three groups randomly: the control group, the experimental group and the intervention group. In the control group, laparotomy were performed, duodenum and pancreas were flipped only. In the experimental group, acute necrotizing pancreatitis model was induced in rats by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. In the intervention group, methylprednisolone (30mg/kg) was injected into rump musle of rats after models were developed. At 6 and 12 hours after model were developed, MMP-9 expression was detected in brain by means of immunohistochemistry and MMP-9 in serum was quantitated in serum by ELISA kits. Serum GFAP and IL-6 were also quantitated using ELISA kits. The severity of pancreatitis was determined by local pathological lesion (gross and histopathologic scoring ). The brain tissure water content, Evans Blue concentration (permeability of BBB), MPO activity were detected, too. The effect of methylprednisolone were observed at the same time.Results1. The expression of MMP-9 in brain reinforced at 6 hours after ANP model induction, and more at 12 hours(P<0.05).2. The MPO activity in brain increased at 6 hours after ANP model induction and more at 12 hours(P<0.01).3. The concentration of Evans Blue in brain increased at 6 hours after ANP model induction, and more at 12 hours(P<0.05).4. The MMP-9, GFAP and IL-6 in serum increased at 6 hours after ANP model induction, and more at 12 hours(P<0.05).5. Intervention of methylprednisolone decreased water content, MMP-9 expression, MPO activity and concentration of Evans Blue in brain and MMP-9, GFAP, IL-6 in serum at6 hours after ANP model induction(P<0.05). But at 12 hours, MMP-9 expression in brain and GFAP in serum did not decrease so obviously(P>0.05).Conclusions1. Brain damage occurs at 6 hours after ANP model induction in rats, and is more severe at 12 hours.2. MMP-9 perhaps is involved in the development of acute necrotizing pancreatitis associated brain damage.3. Serum GFAP is a potential biochemical marker for diagnosis of acute necrotizing pancreatitis associated brain damage.4. The intervention of methylprednisolone may attenuate the severity of acute necrotizing pancreatitis associated brain damage on the early stage of ANP.