Mechanism and therapy of ventilator-induced lung injury

呼吸机所致肺损伤的机制及治疗

• 批准号: 17591629
• 负责人: NISHINA Kahoru
• 金额: $ 1.34万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591629/
• 关键词: acute lung injury; ventilation; alveolar epitheium; cytokine; fluorocarbon; neutrophil; shear stress

The aim of our study was to explore mechanism of ventilator-induced lung injury and seek its therapy. Acute lung injury was induced by high tidal volume ventilation (15 mL/kg) in rabbits (Injury Group). In Non-injury Group, the lungs were mechanically ventilated by standard volume (8 mL/kg). In Injury Group, oxygenation and lung compliance were decreased 2 hrs after the start of ventilation. Furthermore, plasma cytokine (IL-6) level was increased. Light microscopic examination showed that high tidal volume ventilation caused lung edema and infiltration of neutrophils into alveolar spaces. Intratracheal administration of fluorocarbon to the injured lungs attenuated aggravation of oxygenation, lung compliance, and histological damage, but failed to inhibit cytokine production. The second study used cultured alveolar epithelial type II cells (AEC-II). Shear stress for 2 hrs did not change conformation of AEC-II (A549), but increased expression of IL-6 and MCP-1 mRNA. Treatment of fluorocarbon inhibited shear stress-induced mRNA expression of the inflammatory cytokines. Our studies suggest that fluorocarbon improved oxygenation and pathological changes in in-vivo lung injury model, and attenuation of inflammation with fluorocarbon did not play an important role in the mechanism of improvement.

本研究的目的是探讨呼吸机相关性肺损伤的发生机制及治疗方法。采用大潮气量通气（15 mL/kg）建立急性肺损伤模型（损伤组）。非损伤组给予标准肺容量（8 mL/kg）机械通气。损伤组在机械通气开始后2 h氧合和肺顺应性下降。此外，血浆细胞因子（IL-6）水平升高。光镜检查显示，大潮气量通气导致肺水肿和中性粒细胞浸润到肺泡腔。损伤肺内给予氟碳化合物可减轻氧合、肺顺应性和组织学损伤的加重，但未能抑制细胞因子的产生。第二项研究使用培养的肺泡上皮II型细胞（AEC-II）。剪切力作用2 h不改变AEC-II（A549）的构象，但增加IL-6和MCP-1 mRNA的表达。氟碳化合物的处理抑制了剪切应力诱导的炎症细胞因子mRNA的表达。我们的研究表明，氟碳化合物改善了在体肺损伤模型的氧合和病理变化，并且氟碳化合物减轻炎症在改善机制中并不起重要作用。

项目成果

Prophylactic and therapeutic approaches to acute lung injury, targeting alveolar epithelial type II cells.

针对肺泡上皮 II 型细胞的急性肺损伤的预防和治疗方法。

• 发表时间: 2007
• 期刊: J Anesth 第21巻・第1号
• 作者: 大島 勉;粕谷由子;村上辰男 他;Oshima T;Oshima T.;麓 正樹;Fumoto M;Fumoto M.;Oshima T;Oshima T.;Oshima T;Oshima T;Oshima T.;Nakada T;斎藤祐司;大島 勉;浦野晃義;長谷洋和;大島 勉;長谷 洋和;Urano A;Nagatani H;麓 正樹;Oshima T;Oshima T.;Oshima T;Oshima T;Oshima T.;Oshima T.;Murakami T;Oshima T;Oshima T.;村上辰男;大島 勉;大島 勉ほか;仁科 かほる
• 通讯作者: 仁科 かほる

Prophylactic and therapeutic approaches to acute lung injury, targeting alveolar epithelial type II cells

针对肺泡上皮 II 型细胞的急性肺损伤的预防和治疗方法

• 发表时间: 2007
• 期刊: Journal of Anesthesia 21-1
• 作者: Kahoru;Nishina
• 通讯作者: Nishina

Expression of CINC-2beta is related to the state of differentiation of alveolar epithelial cells.

CINC-2β的表达与肺泡上皮细胞的分化状态有关。

• DOI: 10.1165/rcmb.2005-0113oc
• 发表时间: 2005
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: Nishina,Kahoru;Zhang,Feijie;Nielsen,LarryD;Edeen,Karen;Wang,Jieru;Mason,RobertJ
• 通讯作者: Mason,RobertJ