Expression and significance of TNF-α and proteins in cerebral tissue of rats with acute necrotizing pancreatitis

Abstract

Objective To investigate the expression of TNF-α messenger RNA(mRNA)and peptide in the brain of rats with acute pancreatitis(AP)and explore its significance in the pathogenesis of pancreatic encephalopathy(PE).Methods Modds of acute necrotizing pancreatitis(ANP,n=16)and acute edematous pancreatitis(AEP,n=16)were induced by injecting sodium taurocholate into the pancreatic duct of male Sprague Dawley rats.Another 16 normal rats were employed to serve as controls.Twelve hours after the induction of AP,the rats in each group were sacrificed and the blood and cerebral spinal fluid(CSF)samples were taken for determining the level of TNF-α by ELISA.TNF-α mRNA and peptide expression in the cerebral tissues was assessed by semiquantitative RT-PCR,Western blotting and immunohistochemistry,respectively.Results TNFF-α concentration in blood and CSF of rats with ANP showed significant elevation as compared with AEP and control grouP(P＜0.05).TNF-α concentration in blood of ANP,AEP and control group were 1065.6pg/ml,577.5pg/ml and 543.8pg/ml,respectively.The concentration in CSF was 820.9pg/ml,307.4pg/ml and 481.6Pg/ml,respectively.TNF-α mRNA expression and its protein level in the cerebra of rats with ANP were significantly greater than that in the other two groups respectively(P＜0.05).Double-labeling and immunohistochemical studies revealed that the protein was located in the microglial cells and neurons in the cerebrum.Conclusion The cerebrum might be one of the organs releasing cytokines during AP.TNF-α is overproduced by both microglial cells and neurons in the cerebrunl and might play an important role in the demyelinization of brain during the early stage of ANP. Key words: Pancreatitis; Tumor necrosis factor; Encephalopathy