Effects of ocreotide on intestinal mucosa in rats with portal hypertensive enteropathy

Abstract

To clarify the effects of long-term ocreotide (a long-acting somatostatin analogue) treatment on mucosal changes in a rat model of portal hypertensive enteropathy, groups of male Swiss albino rats (n=15 each) were randomly assigned to one of three treatment arms. These were: sham laparotomy+twice daily subcutaneous saline 0.5 mL (Group 1); portal hypertension induction+twice daily subcutaneous saline 0.5 mL (Group 2); and portal hypertension induction+subcutaneous ocreotide 100 microg/kg/12h (Group 3). After 12 weeks of treatment, jejunal and ileal tissue specimens were obtained and evaluated histopathologically (villus/crypt ratio, mean diameter of dilated vessels, mucosal edema, and fibromuscular proliferation in the lamina propria) and immunohistochemically (vascular endothelial growth factor (VEGF), von Willebrand factor (F8), and cluster of differentiation 34 (CD34) labelling). In jejunal specimens, the villus/crypt ratio was markedly lower in Group 2 (2.38+/-0.46 microm) than in Group 1 (5.07+/-2.25 microm) or Group 3 (4.97+/-2.19 microm); mean diameter of dilated vessels was markedly higher in Group 2 (43.30+/-5.71 microm) than in Group 1 (33.53+/-4.00 microm) or Group 3 (36.76+/-3.96 microm); mucosal edema and fibromuscular proliferation were universally absent in Group 1 when compared with the other groups. There were statistically significant differences (p<0.05) between Groups 1 and 2 for villus/crypt ratio, mean diameter of dilated vessels, VEGF immunolabelling intensity, and CD34 immunolabelling intensity; between Groups 1 and 3 for mean diameter of dilated vessels, VEGF immunolabelling intensity, and CD34 immunolabelling intensity; and between Groups 2 and 3 for villus/crypt ratio, mean diameter of dilated vessels, and VEGF immunolabelling intensity. In ileal tissue specimens, the villus/crypt ratio was markedly lower in Group 2 (5.51+/-0.67 microm) than in either Group 1 (7.19+/-2.18 microm) or Group 3 (7.62+/-2.58 microm); mean diameter of dilated vessels was markedly higher in Group 2 (46.36+/-4.77 microm) than in either Group 1 (36.43+/-4.57 microm) or Group 3 (41.31+/-4.70 microm); while mucosal edema was absent in Group 1, it was present in Group 2 and Group 3; and fibromuscular proliferation was universally absent. There were statistically significant differences (p<0.05) between Groups 1 and 2 for villus/crypt ratio and mean diameter of dilated vessels; between Groups 1 and 3 for mean diameter of dilated vessels; and between Groups 2 and 3 for villus/crypt ratio, mean diameter of dilated vessels, and VEGF immunolabelling intensity. Together, these findings indicate that ocreotide treatment ameliorates histomorphological changes in a rat model of portal hypertensive enteropathy.