Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS.

中文翻译：

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Lomerizine 通过减少 Ca2+ 流入来抑制巨噬细胞活化，从而减轻 LPS 引起的急性肺损伤

急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是危及生命的肺部疾病，死亡率很高，主要归因于急性和严重的肺部炎症。洛美利嗪 (LMZ) 是一种钙通道阻滞剂，以前用于预防和治疗偏头痛。在这里，我们发现LMZ通过减少脂多糖（LPS）诱导的ALI小鼠的肺水肿、中性粒细胞浸润和促炎细胞因子的产生来抑制炎症反应和肺部病理损伤。在体外实验显示，用LMZ治疗后，巨噬细胞中白细胞介素（IL）-1β、IL-6和肿瘤坏死因子（TNF）-α的表达减弱。LMZ 处理后，p38 MAPK、ERK1/2、JNK 和 NF-κB p65 的磷酸化受到抑制。此外，LPS诱导的Ca2+LMZ 治疗可减少流入，这与抑制促炎细胞因子的产生相关。和L型Ca2+通道激动剂 Bay K8644 (BK) 可以恢复细胞因子的产生。总之，我们的研究表明 LMZ 可以缓解 LPS 诱导的 ALI，并且是治疗 ALI/ARDS 的潜在药物。