Thalidomide effect in endothelial cell of acute radiation proctitis

Abstract

Aim: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats.

Methods: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF).

Results: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower in the endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P<0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3+/-6.8) than in the control group (3.7+/-1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8+/-3.5, P<0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P=0.003).

Conclusion: The mechanisms of acute radiation-induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.

Figures

Figure 1

Immunohistochemical staining of TM (thrombomodulin) expression in the endothelial cells of the mucosa and submucosa. The intensity of TM expression in capillaries is significantly higher in the control group (A) and thalidomide group (C) than in the radiation group (B) (× 200).

Figure 2

Immunohistochemical staining of vWF expression in the endothelial cells of the mucosa and submucosa. Both the total number of microvessels and the number of vWF expressing microvessels are markedly higher in the radiation group (B) than in the control group (A), which are attenuated in the thalidomide group (C) (× 200).

Figure 3

Immunohistochemical staining of VEGF expression in the endothelial cells of the mucosa and submucosa. The number of VEGF-positive microvessels and the intensity of VEGF expression were significantly higher in the radiation group (B) than in the control (A) and thalidomide (C) groups (× 200).