Colchicine reduces lung injury in experimental acute respiratory distress syndrome.
Colchicine reduces lung injury in experimental acute respiratory distress syndrome.
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秋水仙碱减少了实验性急性呼吸窘迫综合征中的肺损伤。
DOI：
10.1371/journal.pone.0242318
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Tardif JC
中科院分区：
文献类型：
--
作者：
Dupuis J;Sirois MG;Rhéaume E;Nguyen QT;Clavet-Lanthier MÉ;Brand G;Mihalache-Avram T;Théberge-Julien G;Charpentier D;Rhainds D;Neagoe PE;Tardif JC
急性呼吸窘迫综合征（ARDS）的特点是剧烈的炎症失调导致急性肺损伤（ALI）和呼吸衰竭。ARDS没有有效的药物治疗方法。秋水仙碱是一种低成本、可广泛获得的药物，对治疗炎症状况有效。研究秋水仙碱预处理对油酸致大鼠急性呼吸窘迫综合征的影响。大鼠在静脉注射油酸诱导ALI （150 mg/kg）前给予秋水仙碱（1 mg/kg）或安慰剂治疗3天。四小时后，他们被研究并与假组进行比较。秋水仙碱使肺组织损伤面积减少61%，减少肺水肿，并通过将PaO2/FiO2从66±13 mmHg（平均±SEM）提高到246±45 mmHg，而假动物的PaO2/FiO2为380±18 mmHg。秋水仙碱还能降低PaCO2和呼吸性酸中毒。髓过氧化物酶免疫染色显示，损伤后肺中性粒细胞募集从1.16±0.19%显著增加至8.86±0.66%，秋水仙碱显著降低至5.95±1.13%。治疗也减少了肺NETosis的增加。秋水仙碱治疗并没有减少ALI后的循环白细胞，但中性粒细胞反应性和淋巴细胞群上CD4和CD8细胞表面表达得到恢复。秋水仙碱降低实验性ARDS患者ALI和呼吸衰竭与肺中性粒细胞募集减少和循环白细胞激活减少有关。本研究支持秋水仙碱预防急性呼吸窘迫综合征的临床发展。
The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to acute lung injury (ALI) and respiratory failure. There are no effective pharmacologic therapies for ARDS. Colchicine is a low-cost, widely available drug, effective in the treatment of inflammatory conditions. We studied the effects of colchicine pre-treatment on oleic acid-induced ARDS in rats. Rats were treated with colchicine (1 mg/kg) or placebo for three days prior to intravenous oleic acid-induced ALI (150 mg/kg). Four hours later they were studied and compared to a sham group. Colchicine reduced the area of histological lung injury by 61%, reduced lung edema, and markedly improved oxygenation by increasing PaO2/FiO2 from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg compared to 380 ± 18 mmHg in sham animals. Colchicine also reduced PaCO2 and respiratory acidosis. Lung neutrophil recruitment, assessed by myeloperoxidase immunostaining, was greatly increased after injury from 1.16 ± 0.19% to 8.86 ± 0.66% and significantly reduced by colchicine to 5.95 ± 1.13%. Increased lung NETosis was also reduced by therapy. Circulating leukocytosis after ALI was not reduced by colchicine therapy, but neutrophils reactivity and CD4 and CD8 cell surface expression on lymphocyte populations were restored. Colchicine reduces ALI and respiratory failure in experimental ARDS in relation with reduced lung neutrophil recruitment and reduced circulating leukocyte activation. This study supports the clinical development of colchicine for the prevention of ARDS in conditions causing ALI.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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