Expression of TNF-alpha and VEGF in the esophagus of portal hypertensive rats.

ABSTRACT

AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats. METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M(7), M(14), and M(21)) in which the rats were kiued on the seventh day, the 14(th) d and the 21 d after the complete portal ligation. Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C(7), C(14) and C(21)) corresponding to the models. The expression of TNF-alpha and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique. RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82+/-1.83 vs 11.61+/-0.86 cmH(2)O, 20.90+/-3.27 vs 11.43+/-1.55 cmH(2)O and 20.68+/-2.27 vs 11.87+/-0.79 cmH(2)O respectively, P<0.01), as well as the number (9.3+/-1.6 vs 5.1+/-0.8, 11.1+/-0.8 vs 5.4+/-1.3 and 11.7+/-1.5 vs 5.2+/-1.1 respectively, P<0.01) and the total vascular area (78 972.6+/-3 527.8 vs 12 993.5+/-4 994.8 mum(2), 107 207.5+/-4 6461.4 vs 11 862.6+/-5 423.2 mum(2) and 110 241.4+/-49 262.2 vs 11 973.7+/-3 968.5 mum(2) respectively, P<0.01) of submucosal veins in esophagus. Compared to the corresponding controls, the expression of TNF-alpha and VEGF in M(21) was significantly higher (2.23+/-0.30 vs 1.13+/-0.28 and 1.65+/-0.38 vs 0.56+/-0.30 for TNF-alpha and VEGF respectively, P<0.01), whereas there was no difference in M(7) (1.14+/-0.38 vs 1.06+/-0.27 and 0.67+/-0.35 vs 0.50+/-0.24 for TNF-alpha and VEGF respectively, P>0.05) and M(14) (1.20+/-0.25 vs 1.04+/-0.26 and 0.65+/-0.18 vs 0.53+/-0.25 for TNF-alpha and VEGF respectively, P>0.05). And the expression of TNF-alpha and VEGF in M(21) was significantly higher than that in M(7) (2.23+/-0.30 vs 1.14+/-0.38 and 1.65+/-0.38 vs 0.67+/-0.35 for TNF-alpha and VEGF respectively, P<0.01) and M(14) (2.23+/-0.30 vs 1.20+/-0.25 and 1.65+/-0.38 vs 0.65+/-0.18 for TNF-alpha and VEGF respectively, P<0.01), but there was no difference between M(7) and M(14) (1.14+/-0.38 vs 1.20+/-0.25 and 0.67+/-0.35 vs 0.65+/-0.18 for TNF-alpha and VEGF respectively, P>0.05). CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-alpha and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.