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Treatment of multiple oragn dysfunction syndrom : establisment of endothelial cell targetting therapy

多器官功能障碍综合征的治疗：内皮细胞靶向治疗的建立

基本信息

批准号：
11671170
负责人：
MORISAKI Takashi
金额：
$ 2.3万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671170/
关键词：
MODS endothelial cell angiogenic factor liver injury bFGF VEGF regeneration ミトコンドリア障害 MODS 血管内皮ミトコンドリアアポトーシス

项目摘要

Microcirculatory insufficiency resulting from endothelial cell injury is a main causative factor in sepsis-induced multiple organ dysfunction syndrome, which is a main cause of death in critical care unit. In this study, we sought to determine if endothelial cell growth factor therapy decrease organ injury in sepsis model. In in vitro experiments, we examined whether angiogenic factors such as basic fibroblast growth factor ad vascular endotthelial cell growth factor can Inhibit endothelial cell injury induced by reactive oxygen Intermediates or activated neutrophils. In 3-dimensional culture model, we showed that treatment with bFGF and VEGF could attenuate the decrease in tube formation of endothelial cells. We also demonstrated that anti-oxidative stress reagent such as N-acetyl cystein can Inhibit mitochondrial dysfunction In endothelial cells Induced by activated neutrophils and reactive oxygens such as hydrogen peroxide. In animal sepsis model, we examined the effects of angiogenic factors administration could attenuate the oorgan injury such as liver dysfunction. However we could not show the therapeutic effect of angiogenic factors administration on liver injury in this sepsis model. We are going to use both angiogenic factors and bone marrow cells for treatment of septic liver injury and oragn regeneration in animal model.

内皮细胞损伤导致的微循环功能不全是脓毒症所致多器官功能障碍综合征的主要原因，也是重症监护室死亡的主要原因。在这项研究中，我们试图确定内皮细胞生长因子治疗是否减少脓毒症模型的器官损伤。在体外实验中，我们检测了血管生成因子如碱性成纤维细胞生长因子和血管内皮细胞生长因子是否可以抑制活性氧中间体或活化的中性粒细胞诱导的内皮细胞损伤。在三维培养模型中，我们发现用bFGF和VEGF处理可以减轻内皮细胞管形成的减少。我们还证明了抗氧化应激试剂如N-乙酰半胱氨酸可以抑制由活化的中性粒细胞和活性氧如过氧化氢诱导的内皮细胞线粒体功能障碍。在动物脓毒症模型中，我们研究了血管生成因子的应用可以减轻器官损伤，如肝功能障碍。然而，我们无法证明血管生成因子给药对该脓毒症模型中肝损伤的治疗作用。我们将在动物模型中使用血管生成因子和骨髓细胞来治疗脓毒性肝损伤和器官再生。