PDF(Pubmed)
Abstract：
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.
摘要：
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,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。这里,我们发现LMZ通过减轻肺水肿抑制炎症反应和肺病理损伤,脂多糖（LPS）诱导的ALI小鼠中性粒细胞浸润和促炎细胞因子的产生。体外实验,用LMZ治疗后，白细胞介素（IL）-1β的表达，巨噬细胞中IL-6和肿瘤坏死因子（TNF）-α减弱。p38MAPK的磷酸化,ERK1/2,JNK,LMZ处理后NF-κBp65受到抑制。此外，通过用LMZ处理减少LPS诱导的Ca2流入，这与抑制促炎细胞因子的产生有关。而L型Ca2+通道激动剂BayK8644(BK)可以恢复细胞因子的生成。总之,我们的研究表明,LMZ可减轻LPS诱导的ALI,是治疗ALI/ARDS的潜在药物.
