Aydede Hasan, Seda Vatansever H, Erhan Yamac, Ilkgül Ozer
Department of Surgery, Faculty of Medicine, Celal Bayar University, Manisa, 35290 Faikbey, Turkey.
Acta Histochem. 2009;111(1):74-82. doi: 10.1016/j.acthis.2008.04.004. Epub 2008 Jun 12.
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.
为阐明长效奥曲肽（一种长效生长抑素类似物）长期治疗对门静脉高压性肠病大鼠模型黏膜变化的影响，将雄性瑞士白化大鼠（每组15只）随机分为三个治疗组。分别为：假手术+每日两次皮下注射0.5 mL生理盐水（第1组）；诱导门静脉高压+每日两次皮下注射0.5 mL生理盐水（第2组）；诱导门静脉高压+皮下注射奥曲肽100μg/kg/12小时（第3组）。治疗12周后，获取空肠和回肠组织标本，进行组织病理学评估（绒毛/隐窝比值、扩张血管的平均直径、黏膜水肿和固有层纤维肌增生）和免疫组织化学评估（血管内皮生长因子（VEGF）、血管性血友病因子（F8）和分化簇34（CD34）标记）。在空肠标本中，第2组（2.38±0.46μm）的绒毛/隐窝比值明显低于第1组（5.07±2.25μm）或第3组（4.97±2.19μm）；第2组（43.30±5.71μm）扩张血管的平均直径明显高于第1组（33.53±4.00μm）或第3组（36.76±3.96μm）；与其他组相比，第1组普遍不存在黏膜水肿和纤维肌增生。第1组和第2组在绒毛/隐窝比值、扩张血管的平均直径、VEGF免疫标记强度和CD34免疫标记强度方面存在统计学显著差异（p<0.05）；第1组和第3组在扩张血管的平均直径、VEGF免疫标记强度和CD34免疫标记强度方面存在统计学显著差异；第2组和第3组在绒毛/隐窝比值、扩张血管的平均直径和VEGF免疫标记强度方面存在统计学显著差异。在回肠组织标本中，第2组（5.51±0.67μm）的绒毛/隐窝比值明显低于第1组（7.19±2.18μm）或第3组（7.62±2.58μm）；第2组（46.36±4.77μm）扩张血管的平均直径明显高于第1组（36.43±4.57μm）或第3组（41.31±4.70μm）；第1组不存在黏膜水肿，第2组和第3组存在黏膜水肿；普遍不存在纤维肌增生。第1组和第2组在绒毛/隐窝比值和扩张血管的平均直径方面存在统计学显著差异（p<0.05）；第1组和第3组在扩张血管的平均直径方面存在统计学显著差异；第2组和第3组在绒毛/隐窝比值、扩张血管的平均直径和VEGF免疫标记强度方面存在统计学显著差异。这些研究结果共同表明，奥曲肽治疗可改善门静脉高压性肠病大鼠模型的组织形态学变化。
