A Peptide Inhibitor of Peroxiredoxin 6 Phospholipase A(2) Activity Significantly Protects against Lung Injury in a Mouse Model of Ventilator Induced Lung Injury (VILI).
A Peptide Inhibitor of Peroxiredoxin 6 Phospholipase A(2) Activity Significantly Protects against Lung Injury in a Mouse Model of Ventilator Induced Lung Injury (VILI).
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DOI：
10.3390/antiox10060925
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发表时间：
2021-06-07
期刊：
影响因子：
--
通讯作者：
Chatterjee S
中科院分区：
文献类型：
--
作者：
Fisher AB;Dodia C;Chatterjee S
呼吸机诱导肺损伤(VILI)是一种与机械通气相关的肺损伤综合征，最常用于急性肺损伤(ALI)的治疗，一般继发于使用大于生理潮气量的应用。为了在实验上复制这种综合征，C57BL/6小鼠气管插管，分别以低潮气量(4mL/kg体重)和高潮气量(12mL/kg体重)呼吸6h，低潮气量通气组的肺参数与未通气组(对照组)无明显差异。高潮气量肺泡灌洗液(BALF)中中性粒细胞增多，提示肺部炎症，BALF蛋白和肺干湿重均升高，提示肺水肿，肺组织硫代巴比妥酸反应物质(TBARS)和8-异前列腺素(8-Isoprostanes)增加，提示肺脂质过氧化，肺蛋白羰基增多，提示蛋白氧化。小鼠气管内或静脉注射一种名为PIP-2的9位氨基酸的PIP-2，可显著降低肺损伤的所有参数约50-80%。PIP-2抑制NADPH氧化酶2(NOX2)的激活。我们认为，PIP-2不影响VILI的机械性肺损伤成分，但显着减少继发性炎症成分。
Ventilator induced lung injury (VILI) is a lung injury syndrome associated with mechanical ventilation, most frequently for treatment of Acute Lung Injury (ALI), and generally secondary to the use of greater than physiologic tidal volumes. To reproduce this syndrome experimentally, C57Bl/6 mice were intubated and ventilated with low (4 mL/Kg body weight) or high (12 mL/Kg) tidal volume for 6 h. Lung parameters with low volume ventilation were unchanged from non-ventilated (control) mice. High tidal volume ventilation resulted in marked lung injury with increased neutrophils in the bronchoalveolar lavage fluid (BALf) indicating lung inflammation, increase in both protein in BALf and lung dry/wet weight indicating lung edema, increased lung thiobarbituric acid reactive substances (TBARS) and 8-isoprostanes indicating lung lipid peroxidation, and increased lung protein carbonyls indicating protein oxidation. Either intratracheal or intravenous pretreatment of mice with a 9 amino acid peptide called peroxiredoxin 6 inhibitor peptide-2 (PIP-2) significantly reduced all parameters of lung injury by ~50–80%. PIP-2 inhibits NADPH oxidase type 2 (NOX2) activation. We propose that PIP-2 does not affect the mechanically induced lung damage component of VILI but does significantly reduce the secondary inflammatory component.
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DOI：
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发表时间：
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影响因子：
4.9
作者：
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影响因子：
--
作者：
FISHER, AB;DODIA, C;CHANDER, A
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影响因子：
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