Protective effects of vascular endothelial growth factor on intestinal epithelial apoptosis and bacterial translocation in experimental severe acute pancreatitis.
OBJECTIVE
Bacterial translocation (BT) plays an important role in systemic complications in severe acute pancreatitis (SAP). We recently demonstrated that accelerated apoptosis of intestinal mucosa might have a role in BT. Effects of vascular endothelial growth factor (VEGF) on intestinal epithelial cell apoptosis and BT were investigated in SAP.


METHODS
Severe acute pancreatitis was induced by retrograde injection of sodium deoxycholate into the biliopancreatic duct in rats. Recombinant rat VEGF (2 microg) was injected, and SAP was immediately induced. Eight hours after the induction, serum amylase/lipase levels and apoptosis of ileal mucosa were evaluated. After 18 hours, the villous height of ileum was examined. After 22 hours, hematocrit, pancreatic water content, BT to the mesenteric lymph nodes, plasma plasminogen activator inhibitor 1 levels, and microvessel density in the small intestine were investigated.


RESULTS
Amylase/lipase levels were significantly elevated in SAP, but VEGF did not affect them. Apoptosis of ileal mucosa was accelerated in SAP, and VEGF significantly reduced the apoptosis. Villous height was significantly decreased in SAP, and VEGF significantly improved it. Vascular endothelial growth factor did not affect the hematocrit or pancreatic water content. Bacterial translocation occurred in the SAP group, and VEGF significantly prevented that. Plasminogen activator inhibitor 1 levels were significantly elevated in SAP, and VEGF significantly improved the elevation. Microvessel counts were significantly reduced in SAP, and VEGF significantly increased them.


CONCLUSIONS
These results suggest that VEGF inhibits intestinal epithelial cell apoptosis and subsequent BT in SAP.
Nakajima
Takahiro
T
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kusunoki-cho, Chuo-ku, Kobe, Japan. t.nakajima@S3.dion.ne.jp
Ueda
Takashi
T
Takeyama
Yoshifumi
Y
Yasuda
Takeo
T
Shinzeki
Makoto
M
Sawa
Hidehiro
H
Kuroda
Yoshikazu
Y
D000208:Acute Disease; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018988:Bacterial Translocation / Q000187:drug effects*; D003840:Deoxycholic Acid; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D008643:Mesentery; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012720:Severity of Illness Index; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use
D043925:Angiogenesis Inducing Agents; D005765:Gastrointestinal Agents; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D003840:Deoxycholic Acid