N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.
N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.
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N-乙酰肝素主要通过拮抗组蛋白来减轻小鼠因吸酸引起的急性肺损伤
DOI：
10.1371/journal.pone.0097074
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhao Z;Guan L;Mao L;Li S;Guan X;Chen M;Guo L;Ding L;Cong C;Wen T;Zhao J
急性肺损伤（ALI）是重症监护病房死亡的主要原因。细胞外组蛋白是近年来发现的重要炎症介质。肝素及其衍生物可以通过静电相互作用结合组蛋白。本研究的目的是研究1）细胞外组蛋白在酸吸入引起的ALI发病机制中的作用，以及2）在高剂量下，N-乙酰肝素（NAH）是否比肝素对组蛋白提供更好的保护。用盐酸（HCl）腹腔内滴注法建立小鼠急性肺损伤模型。以死亡率、血气分析、髓过氧化物酶（MPO）活性、肺水肿及病理改变等指标评价ALI的严重程度。肝素/NAH腹膜内给药，每天两次，持续3天或直至死亡。酸吸入引起细胞外组蛋白明显增加。一个显着的相关性之间存在的浓度的HCl吸入和循环组蛋白。肝素/NAH（10 mg/kg）可改善大鼠的死亡率、血气、MPO活性、肺水肿及病理评分。在20 mg/kg的剂量下，NAH仍然提供保护，但是肝素由于出血并发症而倾向于加重损伤。肝素和组蛋白之间的特异性相互作用通过结合测定来验证。总之，高水平的细胞外组蛋白可能是酸吸入引起的ALI的致病因素。通过中和细胞外组蛋白，肝素/NAH可以在中等剂量下提供类似的保护。在高剂量下，NAH提供比肝素更好的保护。
Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction. The purpose of this study was to investigate 1) the role of extracellular histones in the pathogenesis of ALI caused by acid aspiration and 2) whether N-acetyl-heparin (NAH) provides more protection than heparin against histones at the high dose. ALI was induced in mice via intratracheal instillation of hydrochloric acid (HCl). Lethality rate, blood gas, myeloperoxidase (MPO) activity, lung edema and pathological changes were used to evaluate the degree of ALI. Heparin/NAH was administered intraperitoneally, twice a day, for 3 days or until death. Acid aspiration caused an obvious increase in extracellular histones. A significant correlation existed between the concentration of HCl aspirated and the circulating histones. Heparin/NAH (10 mg/kg) improved the lethality rate, blood gas, MPO activity, lung edema and pathological score. At a dose of 20 mg/kg, NAH still provided protection, however heparin tended to aggravate the injury due to hemorrhagic complications. The specific interaction between heparin and histones was verified by the binding assay. In summary, high levels of extracellular histones can be pathogenic in ALI caused by acid aspiration. By neutralizing extracellular histones, heparin/NAH can offer similar protection at the moderate doses. At the high dose, NAH provides better protection than heparin.
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组蛋白的杀菌作用。
影响因子：
15.3
作者：
HIRSCH, J G
通讯作者：
HIRSCH, J G
影响因子：
6.9
作者：
Casu, Benito;Naggi, Annamaria;Torri, Giangiacomo
通讯作者：
Torri, Giangiacomo
影响因子：
4.1
作者：
Gamberucci, A;Fulceri, R;Benedetti, A
通讯作者：
Benedetti, A
影响因子：
3.8
作者：
Ciesla, DJ;Moore, EE;Sauaia, A
通讯作者：
Sauaia, A
影响因子：
4.6
作者：
Nakamura, T;Vollmar, B;Schäfers, HJ
通讯作者：
Schäfers, HJ