The role of trophoblast cell damage and coagulopathy in the pregnant mice models with preeclamsia-like symptoms

滋养层细胞损伤和凝血障碍在子痫前期样症状妊娠小鼠模型中的作用

• 批准号: 15591739
• 负责人: SUGIMURA Motoi
• 金额: $ 2.05万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591739/
• 关键词: pregnancy-induced hypertension; VEGF; phosphatidylserine; mouse model; preeclamsia; 胎盤内血栓; 妊娠中毒症; 光誘発胎盤内凝固; 胎児子宮内発育遅延; マクロファージ; MIF; フォスフアチジルセリン; アンチセンスMIFアデノウイルス; プロテインC; 胎仔発育遅延モデル

In order to investigate whether the hypercoagulable state in intervillous space in placenta can induce the preeclampsia-like symptoms, we have focused on the negatively-charged phospholipid microvesicles (phosphatidylserine/phosphatidylcholine PS/PC) and vascular endothelial growth factor (VEGF). Our previous reports have shown that PS/PC microvesicles induce intrauterine growth restriction and that the lack of cyclin-dependent kinase inhibitor, p57kip2, expression in the fetus and the placenta with higher expression of VEGF_<164> plays a role in the development of preeclamsia-like symptoms in pregnant mice.Here we have established the novel animal experimental models with preeclamsia-like symptoms as follows and the induction of preeclamsia-like symptoms by PS/PC and VEGF indicates that these are related to the pathophysiology of preeclamsia.1)The artificial PS/PC vesicles induce intrauterine growth restriction with elevations of systolic blood pressure. The elevation of plasma TAT and diffuse fibrin depositions in the placentas indicate enhanced thrombin formation and the significant elevations of SBP can be induced by hypercoagulation in placenta.2)The exogenous murine VEGF_<164> induce preeclamsia-like symptoms and hypercoagulation in the placental circulation with a significant elevation of SBP. Anti-VEGF neutralized antibody suppresses the elevation of SBP and histological changes in placentas with diffuse fibrin depositions.These novel animal models established suggest that hypercoagulable state caused by PS/PC derived from activated platelet and VEGF derived from trophblast is important in preeclamsia-like symptoms. The further research on the mechanisms of preeclamsia will be required in these experimental models.

为了探讨胎盘绒毛间隙高凝状态是否可诱发先兆子痫样症状，我们重点研究了带负电荷的磷脂微泡（磷脂酰丝氨酸/磷脂酰胆碱PS/PC）和血管内皮生长因子（VEGF）。我们先前的研究表明PS/PC微泡可诱导胎儿宫内生长受限，而VEGF高表达的胎儿和胎盘中缺乏细胞周期蛋白依赖性激酶抑制剂p57 kip 2的表达<164>在妊娠小鼠先兆子痫样症状的发生中起作用。PS/PC和VEGF的相似症状表明这些与先兆子痫的病理生理学有关。1）人工PS/PC囊泡诱导子宫内生长受限，伴随收缩压升高。血浆达特升高和胎盘中弥漫性纤维蛋白沉积表明凝血酶形成增强，胎盘高凝可导致SBP显著升高。2）外源性小鼠VEGF_<164>可诱导先兆子痫样症状和胎盘循环高凝，SBP显著升高。抗VEGF中和抗体可抑制收缩压的升高和胎盘弥漫性纤维蛋白沉积的组织学改变，这些新的动物模型的建立提示活化血小板来源的PS/PC和滋养层细胞来源的VEGF引起的高凝状态在先兆子痫样症状中起重要作用。在这些实验模型中，先兆子痫的发病机制有待进一步研究。

项目成果

Exogenous vascular endothelial growth factor can induce preeclampsia-like symptoms in pregnant mice.

外源性血管内皮生长因子可诱发妊娠小鼠先兆子痫样症状。

• 发表时间: 2005
• 期刊: Semin Thromb Hemost. 31(3)
• 作者: Murakami Y;Kobayashi T;Omatsu K;Suzuki M;Ohashi R;Matsuura T;Sugimura M;Kanayama N.
• 通讯作者: Kanayama N.

Sensitivity to activated protein C in patients with deep vein thrombosis during early puerperium period.

产褥期早期深静脉血栓患者对活化蛋白C的敏感性分析

• 发表时间: 2005
• 期刊: Acta Obstet Gynecol Scand. 84(8)
• 作者: Ohashi R;Sugimura.M;Kawamura T;Tamura N;Kanayama N
• 通讯作者: Kanayama N

Phosphatidylserine/phosphatidylcholine microvesicles can induce preeclampsia-like changes in pregnant mice.

• DOI: 10.1055/s-2005-872438
• 发表时间: 2005-06
• 期刊: Seminars in thrombosis and hemostasis
• 影响因子: 5.7
• 作者: K. Omatsu;Takao Kobayashi;Yusuke Murakami;Mika Suzuki;R. Ohashi;M. Sugimura;N. Kanayama