Wang Dan-Bo, Zhang Shu-Lan, Niu Hui-Yan, Lu Jing-Ming
Department of Obstetrics and Gynecology, Second Affiliated Hospital of China Medical University, Shenyang 110004, China.
Zhonghua Fu Chan Ke Za Zhi. 2004 Nov;39(11):759-62.
To establish an experimental endometriosis model using nude mouse as a xenographic host for relative biological behavior study of endometriosis.
Nude mice of experimental group were implanted with the late secretory endometrium of patients with endometriosis (n = 24) or without endometriosis (n = 24) into pelvic and abdominal cavities. Nude mice of control group (n = 3) were implanted with the greater omentum. Nude mice were killed at 5, 15 and 30 d randomly to observe the growth of endometriotic lesions. The morphological changes of endometriotic lesions from different sources and at different time points of growth were examined by light microscopy and electron microscopy; the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) of eutopic endometrium and endometriotic lesions were detected by RT-PCR method, and the expressions of steroid hormone receptors by immunohistochemistry method.
Endometriotic lesions were found from 5 d with rich blood supply, endometrial glands and stroma under light microscope. And the adhesion to mouse tissues became more severe with time. Under electron microscope, proliferation and infiltration of inflammatory cells were most striking at 15 d. At 30 d the organellae of gland cells were disappeared and there was nuclear chromatin aggregation with apoptosis tendency, but secretory granules still could be seen. The expressions of VEGF and MMP-9 mRNA were increased in endometriotic lesions compared with eutopic endometrium (P < 0.05), and were strongest at 15 d (EM group: 1.11 +/- 0.13/1.00 +/- 0.11; NEM group: 1.10 +/- 0.11/0.99 +/- 0.08) and decreased at 30 d (EM group: 0.85 +/- 0.11/0.77 +/- 0.13; NEM group: 0.86 +/- 0.14/0.76 +/- 0.11). Immunochemistry revealed the positive rate of estrogen and progestogen receptors at 30 d (EM group: 4/8 and 4/8; NEM group: 5/8 and 4/8) was lower than that at 5 d (EM group: 7/8 and 7/8; NEM group: 8/8 and 7/8) and 15 d (EM group: 7/8 and 7/8; NEM group: 7/8 and 8/8), and the expressions of steroid hormone receptors were mostly weak. There was no differences in expression of VEGF and MMP-9 mRNA, estrogen and progestogen between endometriotic lesions implanted with normal endometrium and endometrium from patients with endometriosis.
The nude mouse is an appropriate model for the study of the early phase of endometriosis, and the genesis and development of endometriotic lesions are similar to that of human endometriosis. Endometriosis is associated with multiple factors.
以裸鼠作为异种移植宿主建立实验性子宫内膜异位症模型，用于子宫内膜异位症相关生物学行为研究。
将实验组裸鼠（n = 24）分别植入子宫内膜异位症患者（n = 24）或非子宫内膜异位症患者（n = 24）的分泌晚期子宫内膜至盆腔和腹腔。对照组裸鼠（n = 3）植入大网膜。分别于5、15和30 d随机处死裸鼠，观察异位内膜病灶的生长情况。采用光镜和电镜观察不同来源及不同生长时间点异位内膜病灶的形态学变化；采用RT-PCR法检测在位内膜和异位内膜病灶中血管内皮生长因子（VEGF）和基质金属蛋白酶-9（MMP-9）的表达，采用免疫组织化学方法检测类固醇激素受体的表达。
光镜下5 d即可见异位内膜病灶，血供丰富，可见子宫内膜腺体和间质，且随着时间推移与小鼠组织的粘连愈发严重。电镜下，15 d时炎性细胞增殖和浸润最为明显。30 d时腺细胞细胞器消失，出现核染色质聚集并有凋亡倾向，但仍可见分泌颗粒。与在位内膜相比，异位内膜病灶中VEGF和MMP-9 mRNA表达增加（P < 0.05），15 d时最强（异位内膜组：1.11±0.13/1.00±0.11；非异位内膜组：1.10±0.11/0.99±0.08），30 d时降低（异位内膜组：0.85±0.11/0.77±0.13；非异位内膜组：0.86±0.14/0.76±0.11）。免疫组织化学显示，30 d时雌激素和孕激素受体阳性率（异位内膜组：4/8和4/8；非异位内膜组：5/8和4/8）低于5 d（异位内膜组：7/8和7/8；非异位内膜组：8/8和7/8）和15 d（异位内膜组：7/8和7/8；非异位内膜组：7/8和8/8），类固醇激素受体表达大多较弱。植入正常子宫内膜和子宫内膜异位症患者子宫内膜的异位病灶中VEGF和MMP-9 mRNA、雌激素和孕激素表达无差异。
裸鼠是研究子宫内膜异位症早期阶段的合适模型，异位内膜病灶的发生发展与人类子宫内膜异位症相似。子宫内膜异位症与多种因素有关。
