Functional analysis of macrophage in placental coagulation and intrauterine growth restriction

巨噬细胞在胎盘凝血和宫内生长受限中的功能分析

• 批准号: 12671590
• 负责人: SUGIMURA Motoi
• 金额: $ 1.54万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671590/
• 关键词: macrophage; MIF; phosphatidylserin; antisense MIF adenovirus; protein C; intrauterine growth restriction model in mice; 胎盤内凝固; 胎盤マクロファージ; 子宮内胎児発育遅延; recombinant adenovirus; macrophage; IUGR

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.

本研究首先建立了磷脂酰丝氨酸（phosphatidylserin，PS）诱导的宫内生长受限（intrauterine growth restriction，IUGR）小鼠模型，为研究胎盘巨噬细胞功能奠定基础。在PS诱导的IUGR小鼠模型中，外源性抗凝剂Annexin V、活化蛋白C和肝素均能显著抑制IUGR小鼠的生长受限，提示该模型与PS引起的高凝状态有关。携带反义巨噬细胞移动抑制因子（MIF）cDNA的重组腺病毒载体能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。

项目成果

T.Matsuura, M.Sugimura: "Anti-macrophage inhibitory factor antibody inhibits PMSG-hCG-induced follicular growth and ovulation in mice"Am J Assist Reprod Genet. 19(12). 591-595 (2002)

T.Matsuura、M.Sugimura：“抗巨噬细胞抑制因子抗体抑制 PMSG-hCG 诱导的小鼠卵泡生长和排卵”Am J Assist Reprod Genet。

M.Sugimura et al.: "Intraplacental Coagulation in Intrauterine Growth Restriction - Cause or result?"Seminarin Thrombosis and Hemostasis. (in press). (2001)

M.Sugimura 等人：“子宫内生长受限中的胎盘内凝血 - 原因还是结果？”血栓和止血研讨会。

N.Kanayama: "Deficiency in p57 Kip2 expression induces preeclampsia-like symptoms in mice"Mol Hum Repro. 8(11). 1129-1135 (2002)

N.Kanayama：“p57 Kip2 表达缺陷会诱发小鼠先兆子痫样症状”Mol Hum Repro。

T.Iwaki, M.sugimura: "Recombinant adenovirus vector bearing antisense macrophage migration inhibitory factor cDNA prevents acute lypopolysaccharide induced liver failene in mice"Laboratory Investigation. (in press). (2003)

T.Iwaki、M.sugimura：“携带反义巨噬细胞迁移抑制因子 cDNA 的重组腺病毒载体可预防小鼠急性脂多糖诱导的肝衰竭”实验室研究。