Effect of ischemic preconditioning on pancreatic regeneration and pancreatic expression of vascular endothelial growth factor and platelet-derived growth factor-A in ischemia/reperfusion-induced pancreatitis.
Ischemic preconditioning has been shown to protect several organs from ischemia/reperfusion-induced injury. In the pancreas, protective effect of ischemic preconditioning has been shown against pancreatitis evoked by ischemia/reperfusion, as well as by caerulein. However, the effect of ischemic preconditioning on the course of acute pancreatic is unclear. The aim of our study was to evaluate the influence of ischemic preconditioning on pancreatic regeneration and pancreatic presence of platelet-derived growth factor-A (PDGF-A) and vascular endothelial growth factor (VEGF) in the course of ischemia/reperfusion-induced pancreatitis.


METHODS
In male Wistar rats, ischemic preconditioning of the pancreas was performed by short-term clamping of celiac artery (twice for 5 min with 5 min interval). Acute pancreatitis was induced by clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 and 21 days after the start of reperfusion. Severity of acute pancreatitis and pancreatic regeneration were determined by biochemical and morphological examination, expression of growth factors was determined by immunohistochemical analysis.


RESULTS
In ischemia/reperfusion-induced pancreatitis, the pancreatic damage reached the maximal range between the first and second day of reperfusion, and was followed by subsequent pancreatic regeneration. Ischemic preconditioning alone caused mild passing pancreatic damage and an increase in plasma concentration of pro-inflammatory interleukin-1 and anti-inflammatory interleukin-10. Ischemic preconditioning applied before ischemia/reperfusion-induced pancreatitis reduced morphological and biochemical signs of the pancreatitis-evoked pancreatic damage and accelerated pancreatic regeneration. This effect was associated with improvement of pancreatic blood flow. Ischemic preconditioning, ischemia/reperfusion-induced pancreatitis and their combination increased the presence of VEGF in acinar and islet cells, and immunostaining for PDGF-A in blood vessels. This effect was maximally pronounced after combination of ischemic preconditioning plus pancreatitis and occurred earlier than after pancreatitis alone.


CONCLUSIONS
Ischemic preconditioning reduces pancreatic damage and accelerates pancreatic healing in the course of ischemia/reperfusion-induced pancreatitis. This effect is associated with the increase in plasma concentration of anti-inflammatory interleukin-10, improvement of pancreatic blood flow and alteration of pancreatic immunohistochemical expression of PDGF-A and VEGF.
Dembiński
A
A
Department of Physiology, Jagiellonian University Medical College, Kraków, Poland. mpdembin@cyf-kr.edu.pl
Warzecha
Z
Z
Ceranowicz
P
P
Dembiński
M
M
Cieszkowski
J
J
Pawlik
W W
WW
Tomaszewska
R
R
Konturek
S J
SJ
Konturek
P C
PC
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D019194:Ischemic Preconditioning; D008049:Lipase / Q000097:blood; D008297:Male; D010179:Pancreas / Q000098:blood supply* / Q000473:pathology / Q000502:physiology; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D015427:Reperfusion Injury; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D016753:Interleukin-10; D004247:DNA; D008049:Lipase