铁暴露下gpr30与子宫内膜异位囊肿恶性变的关系研究

Endometriosis is a common gynecological disease, malignancy rate increased gradually with the increasing incidence of the disease. .High level of estrogen are one of the most important risk factors of the malignant transformation of endometriosis. Estrogen with receptor binding and then execute its role, but related studies confirm that the nuclear receptor expression are downregulated or even absent in the process of ectopic endometrial malignancy. gpr30 is a newly discovered membrane estrogen receptor and still can mediate the biological effect of estrogen in the nuclear receptor-negative cells. In addition, a large number of studies have confirmed that iron overload leads to malignant. Endometriosis cyst filled with iron metabolism, and these products have any impact on endometriosis and the mechanism all Lack of relevant researchs. . In previous experiments we found: gpr30 was significantly increased after endometrial malignancy, and repeatedly iron microinjection leaded to atypical variant of rat ovarian epithelial cells. Further literature review found that: gpr30 with some iron metabolisms have a close relationship at the molecular level. Therefore, the study of gpr30 impact on ectopic endometrial malignancy and the possible mechanism in the iron exposed inflammatory microenvironment maybe very important to the prevention, diagnosis and treatment of the disease.

子宫内膜异位症的恶变率逐年上升，其病因及发病机制不明，严重威胁女性健康。. 高水平雌激素是子宫内膜异位症恶变的危险因素，但相关研究发现：异位子宫内膜恶变过程中核受体表达下调甚至缺失。gpr30是新型膜雌激素受体，在核受体表达阴性的细胞中仍可介导雌激素生物学作用，我们前期对良恶性异位内膜的研究也初步印证了这一现象。但gpr30在异位内膜恶变前后的功能及机制究竟如何？国内外尚无相关报道。因此，本课题拟建立良恶性的子宫内膜异位症小鼠模型，进一步研究gpr30的表达及功能，并结合异位内膜铁暴露的炎性微环境，通过干扰gpr30表达水平及铁剂微注射等手段，对其可能机制进行初步探索，以期及早发现异位内膜的恶变，并进一步了解其发生发展机制、提高患者生存率及生存质量。

子宫内膜异位症的恶变率逐年上升，其病因及发病机制不明，严重威胁女性健康。高水平雌激素是子宫内膜异位症恶变的危险因素，但相关研究发现：异位子宫内膜恶变过程中核受体表达下调甚至缺失。gpr30是新型膜雌激素受体，在核受体表达阴性的细胞中仍可介导雌激素生物学作用，在前期工作中，我们在良恶性异位内膜的研究也初步印证了这一现象。但gpr30在异位内膜恶变前后的功能及机制究竟如何？国内外尚无相关报道。因此，本项目通过建立良、恶性的子宫内膜异位症小鼠模型，进一步研究了gpr30的表达及功能，并结合异位内膜铁暴露的炎性微环境，通过干扰gpr30表达水平及铁剂微注射等手段，对其可能机制进行了初步探索。通过研究发现，gpr30及铁代谢相关产物Fn、Tf、TfR、IRP的基因、蛋白水平，在恶性异位子宫内膜及子宫内膜异位症相关卵巢癌的表达水平明显增高；gpr30的基因和蛋白水平在铁剂诱导的非典型变异位子宫内膜中分别为0.831± 0.003OD、0.838±0.001OD,均明显高于正常异位内膜(P<0.05)。gpr30在恶性异位子宫内膜的表达与PI3K/AKT、血管生成因子VEGFA/VEGFC具有相关性（p=0.002/ p=0.001）。这些研究结果表明局部铁代谢物积累可诱导异位子宫内膜恶变倾向，上调新型膜雌激素受体gpr30、并进一步影响癌基因PI3K/AKT及血管生成因子VEGFA/VEGFC的表达可能为其途径之一。铁代谢物与gpr30在恶变异位子宫内膜的深入关系仍需进一步探索。