从EVT启动的子宫螺旋动脉重塑探讨寿胎丸治疗复发性流产的作用机制

Successful remodeling of uterine spiral arteries (SPA) is essential to the supply of adequate blood to placenta to maintain gestation as well as effective pregnancy. Meanwhile, failure of this process results in the decline in placental substance exchange capacity and has closely.associated with recurrent spontaneous abortion. Moreover, extravillous trophoblast (EVT) cells play the most essential role to trigger SPA remodeling, by invading the uterine spiral arteries, as well as inducing apoptosis of endothelial cells and smooth muscle cell. It has been.proved that Shou tai wan is effective in treatment of recurrent spontaneous abortion. “Women with two months’ pregnancy can avoid miscarriage by taking Shou tai wan”. It is by and at this right moment that EVT are invading uterine decidual layer as well as SPA is remodeling from placenta peripheral. Thus the project speculates that the mechanism of Shou tai wan in treatment of recurrent.spontaneous abortion may lie in that Shou tai wan might have involved in SPA remodeling. The study intends to investigate the influence of Shou tai wan on SPA remodeling and pregnant rate by CBA mice, and the influence of Shou tai wan on EVT invading capacity and the apoptosis of endothelial cells （BEC） and smooth muscle cell (SMC) by establishing the EVT and BEC/SMC co-culture model. Furthermore, the.study intends to investigate the mechanism of how Shou tai wan promots SPA remodeling by studying Fas/Fasl induced BEC and SMC apoptosis, as well as the mechanism of Shou tai wan in“promoting the absorption of essence from maternal to fetus circulation”. This study will provide theoretical evidence for clinical application of Shou tai wan in treatment of recurrent spontaneous abortion.

子宫螺旋动脉（SPA）重塑对保障胎盘血液灌注，维持妊娠具有重要作用。SPA重塑障碍导致胎盘物质交换力下降，与复发性流产的发生密切相关。绒毛外滋养细胞（EVT）向SPA侵袭并诱导血管内皮细胞（BEC）和平滑肌细胞(SMC)凋亡是启动SPA重塑最重要的环节。寿胎丸治疗复发性流产临床疗效确切，“凡受妊之妇，于两月之后徐服一料，必无流产之弊”，此时恰为EVT侵袭子宫蜕膜层，SPA重塑的重要时期，故推测寿胎丸治疗复发性流产的机制可能在于其参与了SPA重塑。本课题①以寿胎丸干预自发性流产小鼠，评价其对SPA重塑和妊娠结局的影响；②建立EVT与BEC/SMC共培养模型，研究寿胎丸对EVT侵袭力、BEC和SMC凋亡的影响；③从Fas/Fasl介导的BEC和SMC凋亡途径研究寿胎丸促进SPA重塑的作用机制。进而，探讨寿胎丸使胎“善吸母之气化”治疗复发性流产的理论基础，为临床应用其防治复发性流产提供理论证据。

子宫螺旋动脉（SPA）重塑对保障胎盘血液灌注，维持妊娠具有重要作用。SPA重塑障碍导致胎盘物质交换力下降，与复发性流产的发生密切相关。绒毛外滋养细胞（EVT）向SPA侵袭并诱导血管内皮细胞（BEC）和平滑肌细胞(SMC)凋亡是启动SPA重塑最重要的环节。寿胎丸治疗复发性流产临床疗效确切，“凡受妊之妇，于两月之后徐服一料，必无流产之弊”，此时恰为EVT侵袭子宫蜕膜层，SPA重塑的重要时期，故推测寿胎丸治疗复发性流产的机制可能在于其参与了SPA重塑。本课题①以寿胎丸干预自发性流产小鼠，评价其对SPA重塑和妊娠结局的影响；②建立了EVT与BEC/SMC共培养模型，研究寿胎丸对EVT侵袭力、BEC和SMC凋亡的影响；③并从Fas/Fasl介导的BEC和SMC凋亡途径研究寿胎丸促进SPA重塑的作用机制。进而，初步揭示了寿胎丸一方面促进EVT细胞MMP-2、9蛋白表达，增强细胞侵袭力；另一方面，MMP-2、9表达的增加亦促进了FasL的分泌，从而促进绒毛外滋养细胞通过Fas/FasL系统诱导BEC/SMC的凋亡，改善子宫螺旋动脉重塑。阐明了寿胎丸使胎“善吸母之气化”治疗复发性流产的理论基础，为临床应用其防治复发性流产提供理论证据。