人胎盘抗凝蛋白变体对子痫前期模型鼠抗凝治疗的研究

Human Annexin V derivate's antithrombotic effection on a preeclampsia mice model induced by phosphatidylcholine /phosphatidylcholine microvasicles

目的:研究人胎盘抗凝蛋白变体(hAND)对磷脂酰丝氨酸/磷脂酰胆碱(PS/PC)诱导的具有胎盘广泛性微血栓子痫前期(PE)模型鼠的抗凝治疗疗效。方法:将48只妊娠ICR鼠随机分为5组:对照组1和2于妊娠5.5~16.5天连续尾静脉分别注射生理盐水(0.1ml/d)和PS/PC(1mg/d);实验组于妊娠5.5~16.5天注射PS/PC,同时于妊娠6.5~16.5天尾静脉注射Annexin V(A5,5μg/d)(A5组),或hAND(2.5μg/d)(hAND组1)或hAND(5μg/d)(hAND组2)。于125天观察5组的血压、尿蛋白、胎盘重、胎仔重、死胎数、血小板计数、血浆凝血酶-抗凝血酶复合物(TAT)和抗凝血酶Ⅲ(ATⅢ)含量变化,并分析胎盘、肝、肾等脏器纤维蛋白沉积和血栓形成情况。结果:实验组均不同程度地纠正了PE孕鼠的高血压、蛋白尿、胎儿生长受限(FGR)、纤维蛋白微血栓及血液学指标(P<0.05),但大剂量hAND出现了明显的胎盘出血现象。结论:胎盘循环中A5减少致增强的高凝状态及微血栓形成可能是PE模型和FGR的发病机制之一。A5及以其为载体的hAND胎盘局部抗凝治疗PE孕鼠有效,但大剂量hAND不能避免胎盘出血的风险。

Objective: To investigate the therapeutic effects of anticoagulant agents hAND,in a murine PE model induced by PS / PC microvesicles. Methods: The control groups were injected in tail veins everyday from days 5. 5 to 16. 5 of pregnancy with saline 0. 1ml / d or PS / PC 1mg / d. The experiment groups were injected with A5 5μg / d or hAND 2. 5μg / d or 5μg / d from days 6. 5 to 16. 5 of pregnancy at the same time. We evaluated SBP,proteinuria, placental weight,fetal weight,the number of the nubmer of stillbirths,platelet counts,plasma TAT content,antithrombin Ⅲ( ATⅢ) on day 17. 5. Analysis of the placenta,liver,kidney and other organ fibrin deposition and thrombosis. Results: The experiment groups were corrected to varying degrees of hypertension,proteinuria fetal growth restriction,fibrin and hematological parameters in murine PE model. While large doses of hAND induced obvious placental bleeding. Conclusions: The decreased A5 induced enhanced hypercoagulable and micro-thrombosis of placental circulation may be one of the pathogenesis of PE model and FGR.