子宫腺肌病（Adenomyosis,AMS）是妇科的常见病多发病，其发病机制不清。多数学者认为子宫内膜向肌层侵袭性生长是其发病基础，而粘附及侵袭机制在此过程有重要的意义。CD44是一种粘附分子，通过介导细胞与细胞/基质之间的粘附作用，促进肿瘤细胞的迁移，但其在AMS中的研究不多。申请者前期研究发现CD44在AMS患者血清和子宫内膜中均高表达，提示CD44在内膜侵袭过程中起重要作用。为探讨CD44在AMS子宫内膜中表达的意义及其调控机制，本研究在前期研究基础上建立在位及异位内膜体外培养体系，通过干预CD44的表达，观察不同组间子宫内膜迁移/侵袭能力的变化；并利用分子生物学方法证明JNK/AP-1信号通路对CD44表达的调控，及雌激素在JNK/AP-1 /CD44调控途径中的作用。从而为探讨子宫腺肌病的发病机制提供理论依据；为临床研发治疗AMS内膜侵袭的靶向药物提供实验依据。

Adenomyosis is one of the most common gynecologic disorder. Althought pathogenesis is not clear yet, most experts agree with the theory of endomyometrial invagination of the endometrium. The mechanism of adhesion and invasion is important for this process. CD44 is an important adhesion molecular, and plays a major role in tumor cell growth, adhesion, migration. Our previous study found that CD44 were up-regulation both in the serum and endometrium of adenomyosis controlled with control group. We hypothesis that CD44 plays an important role in the adhesion and invasion process of endometrium in adenomyosis. And we hypothesis that the expression of CD44 was regulated by JNK/AP-1/CD44 signaling pathway. So this study intends to detect the gene and protein expression of CD44 in eutopic and ectopic endometrial cells of adenomyosis patients using vitro cell culture system. With the stimulation of estrogen and GnRH-α，continuous observation of changes in the expression of JNK,AP-1 and CD44 are taken on. We are trying to identify the JNK/AP-1/CD4 signaling pathway differentially expressed of CD44 in the endometrium of women with and without adenomyosis, and to explore the potential pathogenesis of adenomyosis. Our study provides the theory basis of invasion and proliferation mechanism of endometrium in adenomyosis, and is expected to develop a new targeted drugs in inhibiting the invasion effect of endometirum.

子宫腺肌病（Adenomyosis,AMS）是妇科的常见病多发病，其发病机制不清。多数学者认为子宫内膜向肌层侵袭性生长是其发病基础，而粘附及侵袭机制在此过程有重要的意义。CD44是一种粘附分子，通过介导细胞与细胞/基质之间的粘附作用及对周围基质的侵袭破坏，促进肿瘤细胞的迁移，但其在AMS中的研究不多。申请者前期研究发现CD44在AMS患者血清中高表达，提示CD44在内膜侵袭过程中起重要作用。我们利用免疫组化对子宫腺肌病患者和正常女性子宫内膜CD44和纤连蛋白的表达进行了定位，并利用酶联免疫反应检测子宫内膜上清中CD44的表达。对子宫腺肌病患者和对照组子宫内膜的上皮和间质细胞进行体外分离培养，利用流式细胞仪分别检测CD44和纤连蛋白的表达。利用Q－RT－PCR技术检测CD44和纤连蛋白在子宫腺肌病患者和对照组在位内膜中基因的表达情况。流式细胞结果显示，在子宫内膜细胞中，上皮细胞约占60%，基质细胞占40%。免疫荧光结果发现，CD44和纤连蛋白在子宫内膜上皮和基质细胞中都主要表达于细胞浆中。酶联免疫反应结果表明，子宫内膜中CD44的表达在子宫腺肌病组和对照组间无显著差异。项目资助发表核心论文1篇，待发表1篇。培养博士生1名， 在读。项目投入经费10万元，支出8.5万元，各项支出基本与预算相符。剩余经费2.3142万元，剩余经费计划用于本项目研究后续支出。