Functional analysis of macrophage in placental coagulation and intrauterine growth restriction

本课题为建立巨噬细胞在胎盘中的功能研究工具，首先建立了磷脂酰丝氨酸（PS）诱导的宫内生长限制（IUGR）小鼠模型。在此基础上，构建了带有正义和反义巨噬细胞迁移抑制因子cDNA的重组腺病毒载体。在ps诱导的IUGR模型中，外源性抗凝剂、膜联蛋白V、活化蛋白C和肝素显著抑制了小鼠模型的生长限制，表明该模型与ps诱导的高凝状态有关。携带反义巨噬细胞迁移抑制因子（MIF） cDNA的重组腺病毒载体显著抑制肝组织损伤，提示反义MIF腺病毒载体通过细胞因子网络调节bcg - lps诱导的肝组织炎症过程。在动物模型中，利用带正义和反义MIF的重组病毒载体，建立了巨噬细胞功能分析系统。

In this research project, in order to establish the research tool for the investigation of function of macrophage in placenta, we established phosphatidylserin (PS)-induced intrauterine growth restriction (IUGR) mice model first. Then, we developed the recombinant adenovirus vector bearing sense and antisense macrophage migration inhibitory factor cDNA.In the PS-induced IUGR model, exogenous anticoagulants, annexin V, activated protein C and heparin inhibited significantly the growth restriction in mice model, indicating that the model is associated with the hypercoagulable state by PS.Furthermore, in the BCG-lipopolysaccharide (LPS) induced liver failure model in mice, recombinant adenovirus vector bearing antisense macrophage migration inhibitory factor (MIF) cDNA suppressed significantly the damage in liver tissue suggesting that antisense MIF adenovirus vector modulates the BCG-LPS-induced inflammatory process through cytokine network in liver tissue.We established the system for the analysis of macrophage functions by using recombinant virus vectors bearing sense and antisense MIF in animal model.