Therapeutic effect of combined protein C pathway factors on acutelung injury

联合Protein C通路因子对急性肺损伤的治疗作用

基本信息

批准号：
18590846
负责人：
TAGUCHI Osamu
金额：
$ 2.57万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Background: Protein S (PS) and activated protein C (APC) have anticoagulant and anti-inflammatory activities. PS may exert anticoagulant activity by favoring the anticoagulant activity of APC and/or by directly inhibiting the prothrombinase complex. The role of PS and the combination of PS and APC on acute lung injury have not been as yet appraised.Objective : The aim of this present study was to evaluate the effect of PS and APC plus PS on acute lung injury in the mouse.Methods : Acute lung injury was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide(LPS)(5mg/kg). Mice treated with saline served as controls. To evaluate the therapeutic effect of PS and APC plus PS, the animals were treated with PS alone, a combination of PS and APC or saline by intraperitoneal injection one hour before LPS instillation. These animals were sacrificed 24 hours after LPS injection and sampling of bronchoalveolar lavage fluid and lung tissue were performed. The in vitro effect of PS on secretion of inflammatory cytokines from alveolar epithelial cells was also assessed.Results : The total cell count and the bronchoalveolar lavage fluid level of total protein, interleukin-6 and monocyte chemoattractant protein-1 were significantly increased in LPS-treated mice compared with controls. Mice with acute lung injury treated with PS and combined therapy of PS plus APC had significantly decreased concentration of interleukin-6 and monocyte chemoattractant protein-1 in bronchoalveolar lavage fluid as compared to untreated animals. Treatment with protein C pathway factors also improved lung pathological changes. PS alone significantly abated the expression of inflammatory cytokines from alveolar epithelial cells.Conclusions : These results suggest that combined administration of protein C pathway factors may be a potential therapeutic strategy for the therapy of acute lung injury.

背景：蛋白质S（PS）和活化蛋白C（APC）具有抗凝剂和抗炎活性。 PS可以通过直接抑制APC的抗凝活性来发挥抗凝活性，直接抑制凝血酶酶复合物。 The role of PS and the combination of PS and APC on acute lung injury have not been as yet appraised.Objective : The aim of this present study was to evaluate the effect of PS and APC plus PS on acute lung injury in the mouse.Methods : Acute lung injury was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide(LPS)(5mg/kg).用盐水治疗的小鼠用作对照。为了评估PS和APC Plus PS的治疗作用，单独使用PS治疗动物，在LPS灌输前一小时通过腹膜内注射将PS和APC或盐水组合在一起。 LPS注射后24小时处置这些动物，并进行支气管肺泡灌洗液和肺组织采样。还评估了PS对肺泡上皮细胞的炎性细胞因子分泌的体外作用。反应：与对照组相比，LPS培养的小鼠中总细胞计数和总蛋白质，白介素6和单核细胞化学剂蛋白1的总蛋白，白介素化学蛋白-6和单核细胞化学剂蛋白1的支气管肺泡灌洗液水平显着增加。与未经治疗的动物相比，用PS和PS Plus APC的急性肺损伤的小鼠在支气管肺泡灌洗液中的白介素-6和单核细胞介脂剂蛋白-1的浓度显着降低。用蛋白质C途径因子处理也改善了肺病理变化。仅PS就显着减轻了肺泡上皮细胞的炎性细胞因子的表达。结论：这些结果表明，蛋白质C途径因子的组合施用可能是治疗急性肺损伤治疗的潜在治疗策略。