Phosphatidylserine/phosphatidylcholine microvesicles can induce preeclampsia-like changes in pregnant mice.
Phosphatidylserine/phosphatidylcholine microvesicles can induce preeclampsia-like changes in pregnant mice.
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DOI：
10.1055/s-2005-872438
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发表时间：
2005-06
影响因子：
5.7
通讯作者：
K. Omatsu;Takao Kobayashi;Yusuke Murakami;Mika Suzuki;R. Ohashi;M. Sugimura;N. Kanayama
中科院分区：
文献类型：
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作者：
K. Omatsu;Takao Kobayashi;Yusuke Murakami;Mika Suzuki;R. Ohashi;M. Sugimura;N. Kanayama
建立了磷脂酰丝氨酸(PS)/磷脂酰胆碱（PC）微泡诱导的小鼠子痫前期样模型。以80% PC和20% PS混合制备PS/PC，悬浮于浓度为10 mg/mL的0.05 M Tris-HCl中。从妊娠第5.5 ~ 16.5天，每天在ICR小鼠尾静脉注射100微升PS/PC （n = 6）和生理盐水（n = 10）作为对照。采用尾袖法测量收缩压（SBP）。第17.5天，采用乙醚麻醉，心脏抽血循环衰竭安乐死。解剖动物，取出胎儿和胎盘。测定胎儿体重和胎盘体重。第17.5天测定血浆抗凝血酶活性（AT）、凝血酶-抗凝血酶复合物（TAT）、血小板计数和蛋白尿。胎盘固定在4%多聚甲醛中进行组织学研究。统计分析采用方差分析和Welch’st检验。注射PS/PC的小鼠显示收缩压显著升高（124比101 mm Hg， p < 0.001）， TAT水平显著升高（23比6.6马克/升，p < 0.05），血小板计数显著降低(88比102 × 10(10)/升；p < 0.05)， AT降低，蛋白尿增加，胎儿体重（1.2比1.3 g, p < 0.0001）和胎盘重量（0.13比0.15 g, p < 0.001）显著降低。经PS/PC注射的小鼠胎盘迷宫层可见弥漫性纤维蛋白沉积。我们已经证明，人工PS/PC囊泡会随着收缩压的升高而诱导宫内生长受限。血浆TAT升高和胎盘弥漫性纤维蛋白沉积提示凝血酶形成增强，收缩压显著升高提示胎盘高凝诱导的子痫前期样改变。
We established a phosphatidylserine (PS)/phosphatidylcholine (PC) microvesicles-induced preeclampsia-like model in mice. PS/PC were prepared by mixing 80% PC and 20% PS, and suspended in 0.05 M Tris-HCl at a concentration of 10 mg/mL. One hundred microliters of PS/PC (n = 6) and saline as a control (n = 10) were injected in tail veins of Institute of Cancer Research (ICR) mice every day from days 5.5 to 16.5 of pregnancy. Systolic blood pressure (SBP) was measured by means of the tail-cuff method. On day 17.5, the mice were anesthetized by diethyl ether and euthanized with the collapse of the circulation by drawing blood from the heart. The animals were dissected and the fetuses and placentas removed. Fetal weight and placental weight were evaluated. Plasma antithrombin activity (AT), thrombin-antithrombin complex (TAT), platelet counts, and proteinuria were measured on day 17.5. Placentas were fixed in 4% paraformaldehyde for histologic studies. Statistical analysis was evaluated by analysis of variance and Welch's t-test. Mice injected with PS/PC showed a significant elevation in SBP (124 versus 101 mm Hg; p < 0.001), a significant increase in TAT levels (23 versus 6.6 mug/L; p < 0.05), a significant decrease in platelet counts (88 versus 102 x 10 (10)/L; p < 0.05), a decrease in AT, an increase in proteinuria, and a significant reduction in fetal weight (1.2 versus 1.3 g; p < 0.0001) and placental weight (0.13 versus 0.15 g; p < 0.001), compared with controls. Placentas of mice injected with PS/PC showed diffuse fibrin depositions in the labyrinth layer. We have demonstrated that the artificial PS/PC vesicles induce intrauterine growth restriction with elevations of SBP. The elevation of plasma TAT and the diffuse fibrin depositions in the placentas indicate enhanced thrombin formation, and the significant elevations of SBP indicate preeclampsia-like changes that can be induced by hypercoagulation in the placenta.