The Change Of Blood Brain Barrier Permeability In Acute Pancreatitis And Its Relative Factors

PartⅠThe pathological injury in different acute pancreatitis model and its relationship with pancreatic MCP-1 expressionObjective:To explore the pathological injury after inducing acute pancreatitis by intrapancreatic ductal injection with different concentration choleate sodium and find the relationship between pancreatic damage and MCP-1 expression.Method:After injection of 5% and 0.5%choleate sodium, we evaluated the pancreatic injury by a score system. Then, we may detect MCP-1 expression by immunohistochemistry and RT-PCR and analyze the relationship between MCP-1 expression and pancreatic inflammation.Result:SAP and MAP had been made by intraductal injection with 5% and 0.5% choleate sodium. Pathological score was significantly different between these two groups(MAP group 2.75±0.86,SAP group 10.15±1.44,p< 0.001). In addition, MCP-1 expression could be found in both these two groups in pancreas, but RT-PCR indicated their levels were different: MCP-1 expressed higher in SAP group than that in MAP group (MAP group 1.37±0.47,SAP group 3.55±0.65,p< 0.001). Correlation analyse showed Pearson correlation coefficient was 0.922,p< 0.001.Conclusion:0.5% choleate sodium can induce mild acute pancreatitis simply and cheaply. MCP-1 may be an important cytokine in the pathogenesis of acute pancreatitis. PartⅡThe change of blood brain barrier permeability in acute pancreatitis Objective:To explore the rule of blood brain barrier permeability change after inducing acute pancreatitis.Method : In different models of acute pancreatitis, we injected Evan's blue intravenously before sacrificing,then we got supernatant fluid after homogenate and centrifuging, then measured its OD value by spectrophotometer. We could get the quantity of Evan's blue in brain by standard curve which reflect the relationship between the quantity of Evan's blue and OD's value.Result:Compared to control group, there was no significant increase of BBB permeability in MAP groups(MAP2h 1.64±0.17 p=0.319; MAP6h 1.69±0.24 p=0.249),However, BBB permeability increased in all SAP groups (SAP2h 1.89±0.12;SAP6h 2.66±0.32;SAP12h 2.91±0.29;SAP242.89±0.69;SAP48h 1.84±0.07,p value are all below 0.05).Conclusion:BBB permeability increase in SAP groups time-dependently.PartⅢThe relationship among pancreatic injury,MCP-1 expression and the change of blood brain barrier permeability in acute pancreatitisObjective:To investigate the relationship among pancreatic injury,MCP-1/TLR4 expression and the change of blood brain barrier permeability in acute pancreatitis.Method:In different models of acute pancreatitis, we used Evan's blue to detect the BBB permeability. The grade of pancreatic injury was measured by a score system and the expression of MCP-1 and TLR4 were measured by immunohistochemistry and RT-PCR.Result:Compared to control group, there was no significant increase of BBB permeability in MAP groups. However, BBB permeability increase in all SAP groups. In the same time, the pathological score of pancreas were significantly higher in SAP groups than those in MAP groups(SAP2h=8.50±1.07; SAP6h=9.75±0.71; SAP2h=8.50±1.07; SAP6h=9.75±0.71; SAP12h10.25±1.28; SAP24h=11.13±1.25; SAP48h=11.13±1.13). Therefore, the expression of MCP-1 and TLR4 only existed in SAP groups.Conclusion:The increase of BBB permeability is related to the severity of pancreatic inflammation and MCP-1 may contribute to the change of BBB permeability. The activation of TLR4 may be the cause of MCP-1 expression increase.PartⅣThe relationship between blood brain barrier permeability and CNS injury in acute pancreatitisObjective:To investigate the relationship between blood brain barrier permeability and CNS injury in acute pancreatitis.Method:In different models of acute pancreatitis, we used Evan's blue to detect the BBB permeability. The grade of CNS injury was measured by expression of GFAP which was an indicator of astrocyte activation. The expression of GFAP was measured by immunohistochemistry and RT-PCR.Result:Compared to control group, there was no significant increase of BBB permeability in MAP groups. However, BBB permeability increased in all SAP groups. In the same time, the expression of GFAP was lower in control group and MAP groups(control group 1.13±0.33;MAP2h=1.00±0.33; MAP6h=1.10±0.55). However, in SAP groups, the level of GFAP expression began to increase in 2 hours and reach the peak value in 12h, then it return to normal(*SAP2h=1.81±0.27; *SAP6h=2.26±0.65; *SAP12h 2.49±0.64; SAP24h=1.05±0.64; SAP48h=1.00±0.61, * means p value <0.05). Therefore, the expression of GFAP related to the BBB permeability.Conclusion:GFAP expression increase transiently which suggest there is no severe injury in CNS during acute pancreatitis. However, BBB permeability may be the cause of GFAP expression.