Regression Of Endometrial Explants In A Rat Model Of Endometriosis Treated With The Angiostatic Compounds Anti-rat Vascular Endotheliar Growth Factor

Object To evaluate the effect of the antirat vascular endothelial growthfactor(anti-rVEGF),danazole,and interferon on the growth of establishedendometriosis lessions in the rat model.Method Sexually mature female Wistar rats were used in this study. Fifty-fiverats of artificial estrus were used in the experimental induction of endometriosis.Endometriosis was induced surgically under anesthesia, acoording to establishedprocedures. One month after the initial surgery, each rat was anesthetized and amidventral laparotomy was performed to determine the state of the endometrialexplants. Each one was measured and photographed during each surgery.Fourty-eight endometriosis rats (EM rats) were started on a treatment program.EM rats were divived randomly into six groups and given the following agentsfor three weeks: danazole, anti-rVEGF ,interferon ,saline solution(control group).Three weeks after the initial treatment, laparotomy was performed and theexplants were measured and photographed. The rats were killed by an overdoseof anesthesia. Each transplant then was excised from the surrounding tissue,trimmed of fat, and embedded in paraffin wax for immunnohistochemical and insitu hybridization(ISH) examination . We investigated mRNA for VEGF by ISH,with immunnohistochemical , we investigated the expression of VEGF,urokionase plasminogen activtor(uPA), plasminogen activtor inhibitor(PAI-1),F-Ⅷ. IIResult In addition to control group, the length of explants were decreased infive other treated groups. The anti-rVEGF united danazole group was found tobe the most effective agents of the regression of endometriosis. In anti-rVEGFgroup, the expression of microvessel densities(MVD), VEGFmRNA, VEGF,uPA was marked decreased, but the level of PAI-1 was the most highest. Wefound significant correlationg between the VEGF and the MVD of the explants.In the anti-rVEGF group, the coefficient of correlationg is –0.786, the P-value is0.005, and in control group is –0.899 and 0.002 respectively. We didn't findrelation between the length of explant and the MVD of the explant.Conclution 1.Anti-rVEGF caused regression of the explant in a rat model ofendometriosis. It could reduced the length of explant, decrease the expression ofMVD, VEGFmRNA, VEGF, Upa, increase the expression of PAI-1. 2. The effect of anti-rVEGF united danazole treatment group better thanonly danazole or anti-rVEGF group. 3. The effect of INF is poor, and INF united danazole had no synergism.