血管内皮细胞生长因子受体在子宫内膜异位症中表达的研究

Expression of vascular endothelial growth factor receptors in the ectopic and eutopic endometrium of women with endometriosis

目的探索血管内皮细胞生长因子(VEGF)受体(Flt1,KDR)在子宫内膜异位症(简称内异症)患者的异位及在位子宫内膜组织中的定位及表达情况。方法分别采用免疫组化、Western印迹法和逆转录聚合酶链反应(RTPCR)检测内异症患者37份在位子宫内膜组织、34份卵巢子宫内膜异位囊肿组织、15份腹膜红色病变组织、4份腹壁子宫内膜异位灶组织,以33例非内异症患者的在位子宫内膜组织作为对照,比较不同组织中Flt1、KDRmRNA及蛋白的阳性表达率和表达强度的差异。结果Flt1、KDR蛋白质除在血管内皮细胞中表达外,还在子宫内膜的腺细胞和间质细胞中表达。Flt1、KDR在内异症患者子宫内膜的阳性表达率分别为94.3%,91.4%,高于卵巢巧克力囊肿(分别为74.3%,77.1%)两者比较P<0.05,与同期非内异症患者在位子宫内膜组织(93.8%,90.6%,P>0.05)的表达率相仿。Flt1、KDR在内异症患者在位子宫内膜组织的核酸水平[吸光度(A)比值]分别为2.4±1.2,3.0±1.4;蛋白质水平灰度值分别为31±17,36±24;同期卵巢巧克力囊肿组织中的核酸水平(A)比值分别为1.5±0.9,1.8±1.0;蛋白质水平灰度值分别为17±6,20±11(P<0.05);对照组子宫内膜组织的核酸水平(A)比值分别为1.9±0.8,2.3±1.3;蛋白水平灰度值为24±18,25±16(P>0.05)。结论VEGF可能通过子宫内膜细胞上的相应受体而发挥一定的生物学作用。内异症患者的异位子宫内膜中Flt1、KDR的表达可能与血管形成相关。

Objective To study the localization and expression of the vascular endothelial growth factor receptors (VEGFR) Fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor (KDR) in human ectopic and eutopic endometrium of patients with endometriosis. Methods Specimens of endometriosis patients, aged (38±8) years, including 37 specimens of entopic endometrium, 34 specimens of ovarian chocolate cyst, 34 specimens of ovarian chocolate cyst, 15 specimens of red peritoneal endometriosis lesions, and 4 abdominal wall endometriosis lesions were collected. Specimens of endometrium of 33 patients with other gynecological diseases, aged (36±8) years, were collected during operation and used as controls. Immunohistochemistry was used to detect the location and expression of Flt-1 and KDR protein in different tissues. Western blotting was used to detect the protein expression of Flt-1 and KDR protein in different tissues. The mRNA expressions of Flt-1 and KDR were detected by RT-PCR. Results Flt-1 and KDR were expressed in the endometrial glandular epithelium and stromal cells besides the endometrial blood vessels. The positive expression rate of Flt-1 and KDR in the ectopic endometrium of endometriosis patients were 94.3% and 91.4% respectively, both significantly higher than those in the ovarian endometrial cyst (74.3% and 77.1% respectively, both P<0.05), and similar to those in the eutopic endometrium of the endometriosis patients (93.8% and 90.6% respectively, both P>0.05). In the eutopic endometrium of the endometriosis patients, the Flt-1 mRNA expression level was 2.4±1.2 and the Flt-1 protein expression level was 31±17, and the KDR mRNA expression level was 3.0±1.4 and the KDR protein expression level was 36±24, all significantly higher than those in the ovarian endometrial cyst (1.5±0.9 and 1.8±1.0 for the Flt-1 and KDR mRNA expressions, and 17±6 and 20±11 for the Flt-1 and KDR protein expressions, all P<0.05), and similar to those in the eutopic endometrium of the non-endometriosis patients (1.9±0.8 and 2.3±1.3 for the Flt-1 and KDR mRNA expressions, and 24±18 and 25±16 for the Flt-1 and KDR protein expressions, all P>0.05) Conclusion VEGF may play certain biological role in the development of endometriosis through VEGFR (Flt-1 and KDR). The expression of Flt-1 and KDR in the endometriotic lesion appears to be associated with neovascualization.