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目的探讨不同类型的血管生成抑制剂对子宫内膜异位症(EMs)病灶生长和血管生成的影响,为从抗血管生成途径治疗EMs提供依据。方法2006年1月至4月取因EMs在解放军总医院行腹腔镜手术患者的在位子宫内膜,种植于重度复合性免疫缺陷病(SCID)小鼠皮下,建立EMs鼠模型。接种后第3周治疗组分别给予腹腔注射血管生成抑制剂重组人内皮抑素YH-16[YH-16组,2mg/(kg.d)]、沙利度胺[thalidomide组,50mg/(kg.d)]、整合素аvβ3单克隆抗体LM609[LM609组,250μg,每周2次]和血管内皮生长因子单克隆抗体[anti-VEGF组,3mg/(kg.d)]。对照组腹腔注射等体积的PBS,连用14d;每隔2d测量异位病灶体积1次;治疗结束后病灶组织称重,并采用免疫组化法测定微血管密度(MVD)。每组SCID小鼠各10只。结果SCID小鼠皮下种植EMs模型内膜存活率高且观察方便;各治疗组病灶体积增长缓慢,并且YH-16组用药后期病灶体积有缩小趋势;YH-16组、LM609组和anti-VEGF组病灶重量及体积低于对照组(P(0.05),光镜下可见治疗组腺体萎缩,结构不完整,间质伴有不同程度的坏死;各治疗组MVD均显著低于对照组(P(0.05)。结论血管生成抑制剂对EMs异位病灶的生长和血管生成有明显的抑制作用,进一步证实了抗血管生成治疗EMs的策略具有可行性。
Objective To investigate the effects of different types of angiogenesis inhibitors on the growth and angiogenesis of endometriosis (EMs) and provide basis for anti-angiogenic therapy of EMs. Methods From January 2006 to April 2006, the eutopic endometrium of EMs patients who underwent laparoscopic surgery in the General Hospital of People ’s Liberation Army (PLA) was implanted subcutaneously in severe combined immunodeficiency disease (SCID) mice to establish EMs murine model. The third week after inoculation, the rats in the treatment group were given intraperitoneal injections of recombinant human endostatin YH-16 [YH-16, 2 mg / (kg · d)], thalidomide, 50 mg / kg .d)], integrin аνβ3 monoclonal antibody LM609 [LM609 group, 250 μg twice weekly], and vascular endothelial growth factor monoclonal antibody [anti-VEGF group, 3 mg / (kg · d)]. The control group was intraperitoneally injected with equal volume of PBS for 14 days. The volume of ectopic lesions was measured every 2 days. The lesions were weighed after the treatment and the microvessel density (MVD) was measured by immunohistochemistry. 10 SCID mice in each group. Results The intimal hyperplasia rate of SCI mice subcutaneously implanted in EMs model was high and the observation was convenient. The volumes of lesions in each treatment group grew slowly, and the volume of lesion in YH-16 group tended to shrink. The volume of YH-16, LM609 and anti-VEGF groups The weight and volume of lesion were lower than that of control group (P <0.05). Under light microscope, glandular atrophy, incomplete structure and interstitial necrosis of gland were observed in treatment group. MVD in each treatment group was significantly lower than that in control group (P 0.05) .Conclusion Angiopoietin inhibitors significantly inhibit the growth and angiogenesis of ectopic EMs, which further confirms the feasibility of antiangiogenic therapy for EMs.