桂楼组分通过RHO GTPases抑制子宫腺肌病内膜细胞EMT的机制研究

子宫腺肌病（AM）为妇科常见疑难病，严重危害健康，疾病进程与子宫内膜上皮-间充质转化（EMT）密切相关，具体机制尚待阐明。RHO GTPases通路在调控EMT发生和细胞侵袭表型获得中起重要作用，“胞宫久瘀至癥”是AM核心病机，课题组创制“通脉化癥汤”临床证实有显效，前期研究发现其核心药对桂枝和重楼各自提取物均能有效抑制AM异位内膜细胞（AMDC）的p-CFL水平、EMT指标和侵袭力，提出假说“桂楼组分可能经RHO GTPases介导CFL磷酸化，调控细胞骨架重排而降低细胞侵袭能力，抑制EMT过程和阻断AM病灶进展”。本研究将筛选桂楼有效组分联用（TCPP）处理AMDC，检测RHO GTPases经CFL介导细胞骨架重排及对EMT、侵袭和迁移的影响，并制备含TCPP中药宫内缓释系统，以宫腔局部给药大鼠AM模型进行验证，明确桂楼组分抑制AM进程的关键靶点，为含中药宫内缓释系统研发奠定基础。

Adenomyosis (AM) is a commonly diagnosed gynecological disease, which threatens women's health. The progression of AM is related to epithelial-mesenchymal transition (EMT) of endometrial cells, but the specific mechanism remains to be clarified. RHO GTPase signaling pathways are important regulators of EMT and cell invasion. The key pathogenesis of AM in traditional Chinese medicine is "Baogong Jiuyu Zhizheng". The "Tongmai Huazheng Decoction" created by our group has been proved to be effective in the treatment of AM. Cinnamomi Ramulus and Paris polyphylla are critical drug pair of the decoction. Our data have showed that both of the extracts of Cinnamomi Ramulus and Paris polyphylla can effectively inhibit the p-CFL level, EMT process and the the invasion of adenomyosis derived cells (AMDC) from ectopic endometrium. Thus, we speculated that active ingredients of Cinnamomi Ramulus and Paris polyphylla may regulate phosphorylation of CFL through RHO GTPases, suppress invasion ability of AMDC by regulating cytoskeleton rearrangement, and block the progression of EMT in AM. In this study, the critical components in Cinnamomi Ramulus and Paris Polyphylla that inhibit invasion and migration ability of AMDC will be identified. The influences of effective ingredients used in combination (TCPP) on cytoskeleton related RHO GTPase pathways, EMT, cell invasion and migration will be elucidated. For the development of sustained release system, we will verify the effects of TCPP containing intrauterine sustained-release system on AM in rats and expound the essential targets of intrauterine administration.