子痫前期（Preeclampsia, PE）病因不明，胎盘浅着床和母体血管内皮损伤是PE公认的两个病理生理变化。近年的研究致力于寻找孕早期使绒毛外滋养细胞（EVT）侵蚀不足致胎盘浅着床的关键分子及其引起母体孕中晚期血管内皮损伤的因素。我们最近的研究发现CD81参与早发型PE发病：它在患者EVT、合体滋养细胞及绒毛间质细胞高表达，而且在外周血清中也升高，还表明CD81抑制EVT侵蚀，也引起内皮细胞激活和成环障碍。另还发现CD81降低滋养细胞中eNOS和p-Akt的表达。我们假设：CD81抑制EVT侵蚀导致胎盘浅着床，孕中晚期由绒毛细胞碎片或外泌体释放到血清中的CD81增加，使内皮细胞PI3K/Akt通路抑制，从而降低eNOS表达，导致内皮细胞功能障碍。本研究将从细胞间分子信息传递和动物实验入手，阐释滋养细胞通过CD81/PI3K/Akt/eNOS导致血管内皮功能障碍，为PE防治提供新靶点。

Trophoblast shallow invasion and maternal vascular endothelial cell spasm are considered as the pathophysiological changes of preeclampsia (PE). Recently, studies have focused on investigating the molecules that are not only contributed to extravillous trophoblast (EVT) shallow invasion and impaired placentation, but also are lead to maternal vascular endothelial cell dysfunction in the second or third trimester. Our previous study found that tetraspanin CD81 is involved in the development of early onset PE: CD81 is significantly upregulated in EVT, syncytiotrophoblasts, the cells in villous core and peripheral sera of patients with PE; Also, CD81 inhibits trophoblast invasion and causes endothelial cell activation and interrupted angiogenesis. In addition, overexpression of CD81 downregulates p-Akt and eNOS expression in trophoblasts. We suppose that the abnormally high expressed CD81 in trophoblasts acts on endothelial cells via microparticles or exosomes to inhibit PI3K/Akt signaling pathway and eNOS expression, then effects vasorelaxation and endothelial cells permeability that are related to PE development. In this project, molecular information transmission between cells and in vivo animal experiments are studied to clarify the trophoblastic CD81 leads to maternal endothelial cell dysfunction through the PI3K/Akt/eNOS mechanism, providing the new targets for prevention and treatment of PE.