Functional analysis of macrophage in placental coagulation and intrauterine growth restriction

本研究首先建立了磷脂酰丝氨酸(PS)诱导的宫内生长受限(IUGR)小鼠模型，为研究胎盘巨噬细胞的功能奠定了基础。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的生长受限，表明该模型与PS诱导的高凝状态有关。此外，在卡介苗-脂多糖(BCG)诱导的小鼠肝衰竭模型中，携带反义巨噬细胞移动抑制因子(MIF)基因的重组腺病毒载体对肝组织的损伤有明显的抑制作用，提示反义MIF重组腺病毒载体通过肝组织细胞因子网络调控BCG-LPS诱导的炎症过程。

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.