重组人内皮抑素对小鼠子宫内膜异位症的影响。

Effect of recombinant human endostatin on endometriosis in mice.

作者信息

Jiang Hong-Qing, Li Ya-Li, Zou Jie

机构信息

Department of Obstetrics and Gynecology, General Hospital of the People's Liberation Army, Beijing 100853, China.

出版信息

Chin Med J (Engl). 2007 Jul 20;120(14):1241-6.

PMID:17697575

Abstract

BACKGROUND

Direct and indirect evidences have suggested that angiogenesis is a prerequisite for the development of endometriosis. Aiming at offering experimental evidences for anti-angiogenesis therapy, we transplanted the eutopic endometrium from patient with endometriosis into the severe combined immunodeficiency disease (SCID) mice, to evaluate the effect of the endostatin on the growth and angiogenesis of the established endometriosis lesions in SCID mice model.

METHODS

Eutopic endometrium of women with endometriosis was transplanted into the SCID mice. The mice were randomized into treatment (n = 10) and control groups (n = 10). Two weeks after the implantation of endometrium fragment, the treatment group was injected with recombinant human endostatin YH-16 into the peritoneal cavity (2 mgxkg(-1)xd(-1)), whereas the control group received equivalent volume of PBS (200 microl/d). The volume of endometriotic lesions in SCID mice was measured every three days, and all the treatment lasted for 14 days. Immunohistochemistry was used to determine microvessel density (MVD) and the expression of VEGF. The results were analyzed by t test and chi(2) test to value the treating effect.

RESULTS

Compared with the control group, growth of endometriosis lesion was reduced in the mice treated with YH-16. Statistically significant differences in the volume and weight of the ectopic lesions were observed between the treatment and the control groups (P < 0.05). Microscopical examination showed that after being treated with YH-16, the volume of the endometrial tissues decreased, the glands depauperated, and the glandular epithelium partially degenerated. Necrotic debris was observed in the endometrial stroma. MVD and expression of VEGF in the treatment group were significantly lower than those in the control group (P < 0.05).

CONCLUSIONS

Recombinant human endostatin affects the maintenance and growth of endometriotic tissues by inhibiting angiogenesis and reducing the expression of VEGF in ectopic lesion. The angiostatic agent may be promising as a therapy for endometriosis.

摘要

背景

直接和间接证据表明血管生成是子宫内膜异位症发生发展的一个先决条件。为了提供抗血管生成治疗的实验证据，我们将子宫内膜异位症患者的在位内膜移植到重症联合免疫缺陷病（SCID）小鼠体内，以评估内皮抑素对SCID小鼠模型中已建立的子宫内膜异位症病灶生长和血管生成的影响。

方法

将子宫内膜异位症患者的在位内膜移植到SCID小鼠体内。将小鼠随机分为治疗组（n = 10）和对照组（n = 10）。在植入子宫内膜碎片两周后，治疗组经腹腔注射重组人内皮抑素YH - 16（2 mg·kg⁻¹·d⁻¹），而对照组给予等量体积的PBS（200 μl/d）。每三天测量SCID小鼠体内子宫内膜异位症病灶的体积，所有治疗持续14天。采用免疫组织化学法测定微血管密度（MVD）和VEGF的表达。通过t检验和χ²检验分析结果以评估治疗效果。

结果

与对照组相比，用YH - 16治疗的小鼠子宫内膜异位症病灶生长减缓。治疗组与对照组异位病灶的体积和重量差异有统计学意义（P < 0.05）。显微镜检查显示，用YH - 16治疗后，子宫内膜组织体积减小，腺体减少，腺上皮部分退变。在子宫内膜间质中观察到坏死碎片。治疗组的MVD和VEGF表达明显低于对照组（P < 0.05）。