赵宇 胡佳宁 杜心怡 王丹菡 卢晓声 胡越 张琼

[摘要] 目的 探討乳脂球表皮生长因子8（MFG-E8）与子宫内膜异位症发生发展的关系，及其对子宫内膜异位症的改善作用。 方法 检测2018年1～6月本院收治的子宫内膜异位症患者与对照组研究对象的腹腔腹水巨噬细胞的吞噬凋亡细胞能力，以及外周血、腹水及异位腹膜中MFG-E8表达差异;雌性SD大鼠随机分为模型组、MFG-E8+模型组、MFG-E8组、PBS+模型组和对照组，观察MFG-E8对异位移植病灶大小的作用，检测模型腹腔微环境中炎症因子白细胞介素-6、肿瘤坏死因子、白细胞介素-1β等的表达变化。 结果 子宫内膜异位症患者腹腔巨噬细胞吞噬功能显著低于正常对照组;子宫内膜异位症患者血清MFG-E8浓度为（0.71±0.08）ng/mL显著低于健康对照志愿者的（0.98±0.11）ng/mL（P<0.05），子宫内膜异位症患者腹水MFG-E8浓度为（0.40±0.05）ng/mL，显著低于健康对照志愿者的（0.59±0.07）ng/mL（P<0.05），异位内膜MFG-E8 mRNA 相对表达量显著低于对照组腹膜组织;重组MFG-E8干预后，能显著减小内异症模型的异位移植病灶体积，同时降低腹腔微环境中炎性细胞因子TNF-α、IL-1β和IL-6水平。 结论 MFG-E8在子宫内膜异位症与对照组人群存在表达差异，MFG-E8能改善子宫内膜异位症。

[关键词] 乳脂球表皮生长因子8;子宫内膜异位症;凋亡;清除

[中图分类号] R711.7          [文献标识码] A          [文章编号] 1673-9701（2020）18-0037-05

The role of milk fat globule epidermal growth factor 8 mediated apoptotic clearance in the pathogenesis of endometriosis

ZHAO Yu1   HU Jia'ning2   DU Xinyi2   WANG Danhan1   LU Xiaosheng1   HU Yue1   ZHANG Qiong1

1.Department of Gynaecology and Obstetrics，the Second Affiliated Hospital & Yuying Childrens Hospital of Wenzhou Medical University， Wenzhou   325000， China; 2.The Second School of Medicine， Wenzhou Medical University， Wenzhou   325000， China

[Abstract] Objective To explore the relationship between milk fat globule epidermal growth factor 8（MFG-E8） and the development of endometriosis， and its improvement effect on endometriosis. Methods The phagocytic ability of macrophages towards apoptotic cells in peritoneal ascites， as well as the expression difference of MFG-E8 in peripheral blood， ascites and ectopic peritoneum， was detected in patients with endometriosis and controls in our hospital from January 2018 to June 2018. Female SD rats were randomLy divided into model group， MFG-E8+model group， MFG-E8 group， PBS+model group and control group. The effect of MFG-E8 on the size of ectopic transplantation lesions was observed. The expression changes of inflammatory factors including interleukin-6，tumor necrosis factor， interleukin-1β in the abdominal microenvironment of the model were detected. Results The phagocytic function of peritoneal macrophages in patients with endometriosis was significantly lower than that in the normal control group. The serum MFG-E8 concentration（0.71±0.08 ng/mL） in patients with endometriosis was significantly lower than that in healthy control volunteers（0.98±0.11）ng/mL（P<0.05）. The ascites MFG-E8 concentration in endometriosis patients was（0.40± 0.05）ng/mL，which was significantly lower than that in healthy control volunteers （0.59±0.07）ng/mL （P<0.05）. The relative expression of ectopic endometrium MFG-E8 mRNA was significantly lower than that of the control group. Intervention with recombinant MFG-E8 can significantly reduce the volume of ectopic transplantation lesions in the endometriosis model and reduce inflammatory cytokines TNF-α，IL-1β and IL-6 levels in the abdominal microenvironment. Conclusion MFG-E8 has different expression between endometriosis and control population， which can improve endometriosis.

[Key words] Milk fat globule epidermal growth factor 8; Endometriosis; Apoptosis; Clearance

子宫内膜异位症（Endometriosis，EMT）是常见的良性妇科疾病，但该病具有侵袭、转移与复发等恶性行为，严重影响育龄期妇女的健康和生活质量[1]，该病的发病率高达30%～50%[2]。但其病因及发病机制仍不清楚。在目前诸多的发病学说中，Sampson的经血逆流学说占主导理论。当经期子宫黏膜碎片逆流入腹腔时，需经历细胞凋亡，凋亡细胞会被其邻近细胞以及招募的吞噬细胞快速有效清除。倘若机体内凋亡细胞不能得到及时清除，凋亡碎片长期存在，则可能引起继发性坏死，释放促炎介质，继而诱发慢性炎症和自身免疫性疾病[3]。

乳脂球表皮生长因子-8（milk fat globule-EGF factor 8，MFG-E8）[4]，最初被发现是作为一个黏附在乳汁脂肪小球膜表面的镶嵌型外周蛋白，参与机体免疫清除过程及其他细胞间相互作用。……