Dong Caijuan, Liu Jielu, Quaranta Alessandro, Jing Xu, Nie Mu, Wheelock Craig E, Murrell Benjamin, Coquet Jonathan M, Bowden Tim Melander, Engstrand Thomas, Adner Mikael
Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiang Su, China.
Front Pharmacol. 2024 Nov 21;15:1503648. doi: 10.3389/fphar.2024.1503648. eCollection 2024.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are important causes of morbidity and mortality in critically ill patients. Gastric contents aspiration is one of the most common causes of ALI/ARDS. To date, there are still no specific and effective pharmacological treatments for ALI/ARDS. Polyvinylalcohol-carbazate (PVAC), a polymer that can bind endogenous aldehydes, neutralize oxidative stress and inhibit inflammatory factors, may be a potential treatment for ALI/ARDS.
A hydrochloric acid (HCl) induced mouse model was employed to assess the effect of PVAC. The changes of lung mechanics, pulmonary edema, histology and immune cells, cytokines, and lipid mediators in bronchioalveolar lavage fluid (BALF) were investigated in HCl-challenged mice.
In the HCl model, PVAC administration alleviated airway hyperresponsiveness and improved pulmonary edema and damage. In addition, it decreased the recruitment of neutrophils to the lung, and inhibited the increase of IL-6, TNF-α and leukotriene B.
These data indicates that PVAC is a potential candidate for the treatment of ALI/ARDS induced by aspiration of gastric acid or for the control of "asthma-like" symptoms in patients with gastroesophageal reflux.
急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是危重症患者发病和死亡的重要原因。胃内容物误吸是ALI/ARDS最常见的病因之一。迄今为止,对于ALI/ARDS仍没有特异性有效的药物治疗方法。聚乙烯醇缩咔唑(PVAC)是一种能够结合内源性醛类、中和氧化应激并抑制炎症因子的聚合物,可能是一种治疗ALI/ARDS的潜在药物。
采用盐酸(HCl)诱导的小鼠模型来评估PVAC的作用。研究了HCl攻击小鼠的肺力学、肺水肿、组织学以及支气管肺泡灌洗液(BALF)中的免疫细胞、细胞因子和脂质介质的变化。
在HCl模型中,给予PVAC可减轻气道高反应性,改善肺水肿和肺损伤。此外,它还减少了中性粒细胞向肺内的募集,并抑制了IL-6、TNF-α和白三烯B的增加。
这些数据表明,PVAC是治疗胃酸误吸所致ALI/ARDS或控制胃食管反流患者“哮喘样”症状的潜在候选药物。