The Role of Monocyte Chemoattractant Protein-1 in Experimental Chronic Pancreatitis Model Induced by Dibutyltin Dichloride in Rats

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Abstract
Recently, dibutyltin dichloride (DBTC) was reported to induce pancreatic fibrosis within 28 days in rats, but it is not clear that the induced condition should be considered chronic pancreatitis. The aim of this study was to clarify whether the pancreatic fibrosis induced by DBTC can be regarded as chronic pancreatitis. Furthermore, we examined the relation of monocyte chemoattractant protein–1 (MCP-1) to the development of pancreatic fibrosis in this model. DBTC solution was injected into the right jugular vein in rats, and biochemical and histologic changes were measured at days 1, 3, 7, 14, and 28. Microscopically, inflammatory cell infiltration was evident in the pancreas at days 1 and 3, mononuclear cell infiltration was observed at days 7, 14, and 28, and pancreatic fibrosis was pronounced 7 days later. At day 28, interstitial fibrosis and atrophy of the gland and ductlike tubular complex had progressed. DBTC produced a significant decrease in the contents of pancreatic protein and amylase, whereas the pancreatic hydroxyproline content increased. Serum and pancreatic MCP-1 concentration significantly increased compared with the control group. Furthermore, the expression of PDGF mRNA in the pancreas increased following the MCP-1 elevation. These results suggest that this experimental model of pancreatic fibrosis induced by DBTC in rats was useful as a chronic pancreatitis model and that MCP-1 may play an important role in the development of pancreatic fibrosis.