Simvastatin attenuates ventilator-induced lung injury in mice.
Simvastatin attenuates ventilator-induced lung injury in mice.
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DOI：
10.1186/cc9209
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Witzenrath M
中科院分区：
文献类型：
--
作者：
Müller HC;Hellwig K;Rosseau S;Tschernig T;Schmiedl A;Gutbier B;Schmeck B;Hippenstiel S;Peters H;Morawietz L;Suttorp N;Witzenrath M
机械通气（MV）是在没有替代方法的情况下挽救急性呼吸衰竭患者生命的干预措施。然而，特别是在损伤前的肺中，即使是保护性通气策略也可能引起呼吸机诱导的肺损伤（VILI），其特征在于肺部炎症和血管渗漏。除了肺保护性通气外，还缺乏减轻VILI的辅助药理学策略。辛伐他汀在体外和体内均表现出抗炎和稳定内皮屏障的特性。对小鼠进行通气（12 ml/kg; 6小时），并进行辛伐他汀（20 mg/kg）或假处理。评估肺微血管渗漏、氧合、肺和全身中性粒细胞和单核细胞计数以及肺和血浆中的细胞因子释放。此外，通过电子显微镜分析肺组织。机械通气诱导VILI，表现为肺微血管渗漏和内皮损伤增加，中性粒细胞和Gr-1高单核细胞的肺募集，以及肺中炎性细胞因子的释放。此外，还观察到VILI相关的全身性炎症，其特征为血液白细胞增多和血浆细胞因子升高。辛伐他汀治疗限制了机械通气小鼠的肺内皮损伤，减轻了肺渗透性过高，阻止了白细胞向肺的募集，降低了肺细胞因子水平并改善了氧合。高剂量辛伐他汀通过减少MV诱导的肺部炎症和高通透性来减轻小鼠VILI。
Mechanical ventilation (MV) is a life saving intervention in acute respiratory failure without alternative. However, particularly in pre-injured lungs, even protective ventilation strategies may evoke ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and vascular leakage. Adjuvant pharmacologic strategies in addition to lung protective ventilation to attenuate VILI are lacking. Simvastatin exhibited anti-inflammatory and endothelial barrier stabilizing properties in vitro and in vivo. Mice were ventilated (12 ml/kg; six hours) and subjected to simvastatin (20 mg/kg) or sham treatment. Pulmonary microvascular leakage, oxygenation, pulmonary and systemic neutrophil and monocyte counts and cytokine release in lung and blood plasma were assessed. Further, lung tissue was analyzed by electron microscopy. Mechanical ventilation induced VILI, displayed by increased pulmonary microvascular leakage and endothelial injury, pulmonary recruitment of neutrophils and Gr-1high monocytes, and by liberation of inflammatory cytokines in the lungs. Further, VILI associated systemic inflammation characterized by blood leukocytosis and elevated plasma cytokines was observed. Simvastatin treatment limited pulmonary endothelial injury, attenuated pulmonary hyperpermeability, prevented the recruitment of leukocytes to the lung, reduced pulmonary cytokine levels and improved oxygenation in mechanically ventilated mice. High-dose simvastatin attenuated VILI in mice by reducing MV-induced pulmonary inflammation and hyperpermeability.
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DOI：
10.1186/cc5050
发表时间：
2006
期刊：
Critical care (London, England)
影响因子：
--
作者：
O'Mahony DS;Liles WC;Altemeier WA;Dhanireddy S;Frevert CW;Liggitt D;Martin TR;Matute-Bello G
通讯作者：
Matute-Bello G
DOI：
10.1164/rccm.200710-1589oc
发表时间：
2008-08-15
影响因子：
24.7
作者：
Chiumello, Davide;Carlesso, Eleonora;Gattinoni, Luciano
通讯作者：
Gattinoni, Luciano
影响因子：
5.7
作者：
Pirat, A;Zeyneloglu, P;Arslan, G
通讯作者：
Arslan, G
影响因子：
158.5
作者：
Amato, MBP;Barbas, CSV;Carvalho, CRR
通讯作者：
Carvalho, CRR
影响因子：
38.9
作者：
Gattinoni, L;Pesenti, A
通讯作者：
Pesenti, A