Song Yunduan, Gou Yusen, Gao Jiameng, Chen Dongxin, Zhang Haibo, Zhao Wenjuan, Qian Feng, Xu Ajing, Shen Yao
Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Department of Clinical Laboratory, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Pharmacol. 2023 Aug 24;14:1236469. doi: 10.3389/fphar.2023.1236469. eCollection 2023.
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 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 Ca influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca 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.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是具有高死亡率的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）是一种先前用于预防和治疗偏头痛的钙通道阻滞剂。在此，我们发现LMZ通过减轻脂多糖（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产生，抑制炎症反应和肺部病理损伤。在实验中，用LMZ处理后，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丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶1/2（ERK1/2）、c-Jun氨基末端激酶（JNK）和核因子κB（NF-κB）p65的磷酸化受到抑制。此外，用LMZ处理可减少LPS诱导的钙内流，这与促炎细胞因子产生的抑制相关。并且L型钙通道激动剂Bay K8644（BK）可恢复细胞因子生成。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。
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