A Study On The Inhibition Of VEGF With Recombinant Human Interferon-α-2b In A Experimental Endometriosis Murine Model

[Objective]: To determine the effects of human interferon(IFN)-α-2b on experimental endometriosis in rats and the differences between intraperitoneal and subcutaneous treatment, this study uses SD rats as experimental models for endometriosis, induced by autotransplantation of endometrium to the peritoneal wall, and measures the vascular endothelial growth factor (VEGF) contained in peritoneal fluid and peripheral blood.[Methods]: 60 virgin, mature, female SD rats were chosen for the study. In estrous stage, the left uterine horn was resected, and the endometrium was dissected from the myometrium. Then the endometrium fragment of endometrial tissue was transplanted beneath the left peritoneal wall. Four weeks later, a second laparotomy was done to choose successful animal models, and 38 rats with experimental endometriosis were randomly divided into 3 groups: the control group (bland control group) 8 rats, group A (intraperitoneal treatment) 15 rats, and group B (subcutaneous treatment) 15 rats. The method of administration is as follows: during the second laparotomy the control group did not receive any treatment; Group A rats were given IFN-α-2b 100,000U by intraperitoneal injection; and Group B were treated with three doses of IFN-α-2b 100,000U every 48 hours by subcutaneous injection, while the first dose was given after the second laparotomy. Laparotomies were performed to each group 4, 6, 8 weeks after the treatment. At the same time the volume of the implant was measured, and 1ml of peritoneal fluid and serum from angular vein was collected respectively, from which supernate fluid was then drawn after centrifuging. The VEGF contained in peritoneal fluid and peripheral blood was measured by enzyme-linked immunosorbent assay (ELISA).[Results]: The model of endometriosis in rats was established successfully with an achievement ratio of 63.3% (38/60). The ectopic endometriotic lesions which were well established and actively growing, appeared as spherical cyst, clear or blood fluid-filled, with microvessels on the surface. Compared with the control group, the size of the ectopic endometriotic lesions of the test groups was significantly smaller after treatment by IFN-α-2b (P＜0.05), and the VEGF content in peritoneal fluid and peripheral blood was significantly decreased. These changes tended to be lasting effects. In addition, there were no significant differences in terms of long term effect between the two ways of administration.[Conclusions]: The method of establishing the model of endometriosis in rat by autotransplantation of endometrium is easy, reliable, economical and with a high achievement ratio. The species is near human and the results of the experiment are reliable. After the treatment by IFN-α-2b the volume of ectopic endometriotic lesions were significantly reduced, and the VEGF contents were decreased in peritoneal fluid and peripheral blood. Therefore we can conclude that IFN-α-2b can directly inhibit the proliferation of endometriotic cells, reduce the local VEGF content, inhibit the angiogenesis of ectopic lesions, and thereby inhibit the growth of ectopic endometriotic lesions. IFN-α-2b is likely to become a new therapy for endometriosis.