重组人内皮抑素治疗子宫内膜异位症鼠模型的实验研究

Endostatin in the Treatment of the Transplanted Model of Endometriosis in SCID Mice

目的:探讨重组人内皮抑素(rh-endostatin)YH-16对子宫内膜异位症(EMS)病灶生长和血管生成的影响,为从抗血管途径治疗EMS提供依据。方法:将EMS患者在位子宫内膜种植于SCID小鼠皮下,建立EMS鼠模型。接种后第3周给予治疗,治疗组(n=10)腹腔注射YH-162mg/kg·d-1,对照组(n=10)腹腔注射等体积磷酸盐缓冲液(PBS),连用14天;每隔3天测量异位病灶体积1次;病灶组织采用免疫组化法测定病灶微血管密度(MVD)及血管内皮生长因子(VEGF)的表达。结果:治疗组病灶体积增长缓慢,并且用药后期病灶体积有缩小趋势;治疗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。治疗组MVD及VEGF表达显著低于对照组。结论:重组人内皮抑素对EMS异位病灶的生长和血管生成有明显抑制作用,其作用机制之一可能是降低了病灶部位VEGF的表达量,进而抑制病灶血管生成达到治疗EMS的目的。

Objective：To investigate the effects of recombinant human endostatin （YH-16） on focus development and angiogenesis of endometriosis （EMS）. Methods; Eutopic endometrium from endometriosis was subcutaneously transplanted into SCID mice,and the EMs mice model was established. Then the mice were randomized into treatment group （ n= 10） received recombinant human endostatin YH-16 （2 mg/kg·d^-1） by intraperitoneal injection;and the control group （ n = 10） received PBS as above. The treatment regimen lasted 14 days. The volumes of EMs lesion were observed every three days. Immunohistochemistry was used to determine microvessel density （MVD） and the expression of VEGF in ectopic tissue. Results： Compared with the control group, growth of endometriosis lesion was reduced in mice treated with YH-16.The differences were statistically significant for the weight and volume of ectopic lesion between the treatment group and the control group （ P 〈 0.05）. On light microscopy, atrophic gland, nonintegrated structure,and some necrosis in stroma can be seen in YH-16 group. MVD and expression of VEGF decreased significantly in the group using YH-16 than the control group （ P〈 0.05）. Conclusions： Recombinant human endostatin can effectively interfere with the maintenance and growth of endometriosis by inhibiting angiogenesis, and endostatin can reduce the expression of VEGF in ectopic lesion. This suggests that the use of angiostatic agents may be promising as a therapy for endometriosis.