Experimental Pancreatitis Results in Increased Blood-brain Barrier Permeability in Rats: a Potential Role of MCP-1

Objective: To measure the changes of blood-brain barrier (BBB) permeability in rats with acute pancreatitis (AP) and to investigate the role of monocyte chemoattractant protein (MCP)-1 expression in this alteration.

Methods: Rat model of severe acute pancreatitis (SAP) and mild acute pancreatitis (MAP) was induced by pancreatic duct infusion of 5% and 0.5% sodium choleate, respectively, and a saline infusion was used in the control. The severity of AP was evaluated by a pathological score system. BBB permeability was detected by Evan's blue tracer and BBB tight junction was assessed by brain occludin expression. Immunohistochemistry and real-time polymerase chain reaction were used to detect MCP-1 expression in the brain. Nifedipine was used as the antagonist of MCP-1.

Results: Compared to the control group, change of BBB permeability was more significant in SAP groups, but not in MAP groups. Occludin level decreased 12 h after SAP induction. Pathological score of SAP group was higher than that in MAP group. BBB opening was associated with pancreatic injury. Brain MCP-1 expression was detected in all the SAP groups, which was correlated with increased BBB permeability, but was not found in the control group or the MAP group. After treatment with nifedipine, brain MCP-1 level decreased and BBB function improved synchronously in SAP groups.

Conclusions: BBB permeability increased in SAP significantly and time-dependently, and was correlated with brain MCP-1 expression. Nifedipine may improve BBB function by inhibiting MCP-1 expression.