傣药麻欠精油抑制子宫内膜异位种植的作用及机制研究

Endometriosis is defined as ectopic growth of endometrial tissues outside the uterine cavity. This benign gynecologic disorder affects 10%-15% of reproductive-aged women and causes symptoms such as infertility, dysmenorrhea, infertility, and chronic pelvic pain. Current medical treatments for endometriosis, such as GnRH agonists and progestins, are effective in relieving the growth of endometriosis and endometriosis-associated pain, yet this pain relief seems to be relatively short term. Because undesirable side effects limit their long-term use, a new therapy for endometriosis is needed. Traditional medicine have positive therapeutic effect on endometriosis with less adverse reaction and multi-target and multi-component pattern. Our previous study showed the essential oil from Dai ethnic medicinal plant Maqian (Zanthoxylum myriacanthum var. Pubescens) induced apoptosis and decreased invasion in ectopic endometrial stromal cells from patients with endometriosis. Maqian essential oil also resulted in suppression of IL-8 production in ectopic endometrial stromal cells treated with TNF-α. Ex vivo experiment demonstrated that Maqian essential oil could repress the development of endometriosis through the preliminary research. Based on our previous study, this project would continue to evaluate the effects of the essential oil from Dai ethnic medicinal plant Maqian on both the human endometriotic stromal cells and the mouse endometriosis-like lesions as a possible therapeutic agent for endometriosis. We also explore its mechanism from the levels of molecule, cell and animal by flow cytometry, Western blotting and RT-PCR. This research will provide more scientific evidence for reasonable exploitation and utilization of Dai ethnic medicinal plant Maqian in Xishuangbanna, China.

子宫内膜异位症（EM）严重危害女性健康，临床药物治疗以激素治疗为主，但存在副作用多、易复发等缺点。传统医药以其多成分、多靶点和作用温和的特点，在EM的治疗中越来越受到重视。本团队前期在结合傣族传统植物药用知识基础上，对西双版纳地区傣族传统药用植物进行抑制子宫内膜异位种植活性筛选，发现麻欠精油具有很好的抑制子宫内膜异位种植活性。本课题拟在前期工作基础上，以原代培养的人子宫异位内膜间质细胞作为体外实验模型，用增强型绿色荧光蛋白转基因和野生型小鼠建立EM体内实验模型，从整体、细胞及分子不同层面探讨麻欠精油对模型病灶组织及细胞增殖、黏附、侵袭、迁移、血管生成和炎症的干预作用，并采用PCR、western blot等方法检测其对NF-κB、AP-1及线粒体凋亡通路等相关信号通路的影响，探讨麻欠精油抑制子宫内膜异位种植的作用和机制，为合理开发利用西双版纳地区的傣药麻欠这一民族药用资源提供科学依据。

子宫内膜异位症（EM）严重危害女性健康，临床药物治疗以激素治疗为主，但存在副作用多、易复发等缺点。传统医药以其多成分、多靶点和作用温和的特点，在EM的治疗中越来越受到重视。本项目在结合傣族传统植物药用知识基础上，对西双版纳地区傣族传统药用植物进行抑制子宫内膜异位种植活性筛选，发现麻欠精油具有很好的抑制子宫内膜异位种植活性。以原代培养的人子宫异位内膜间质细胞作为体外实验模型，用小鼠建立EM体内实验模型，从整体、细胞及分子不同层面探讨麻欠精油对模型病灶组织及细胞增殖、黏附、侵袭、迁移、血管生成和炎症的干预作用。本研究发现麻欠精油可以抑制子宫内膜间质细胞的活力，减少子宫内膜间质细胞的侵袭、迁移和粘附，具有促进细胞凋亡的作用。另外，我们发现麻欠精油具有抗炎作用。进一步研究发现麻欠精油促进细胞凋亡的作用是通过Bcl-2信号级联介导，麻欠精油明显改变子宫内膜间质细胞转录组和蛋白质组，体内动物实验结果发现麻欠精油可以抑制子宫内膜生长。