Recent studies have illuminated that blocking Ca²⁺ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

中文翻译：

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Mibefradil 和 Flunarizine，两种 T 型钙通道抑制剂，保护小鼠免受脂多糖诱导的急性肺损伤

最近的研究表明，阻止 Ca ²⁺流入效应细胞是一种有吸引力的肺损伤治疗策略。我们假设 T 型钙通道可能是急性肺损伤 (ALI) 的潜在治疗靶点。在这项研究中，米贝拉地尔（一种经典的 T 型钙通道抑制剂）的药理活性在脂多糖 (LPS-) 诱导的 ALI 小鼠模型中进行了评估。在 LPS 攻击的小鼠中，米贝拉地尔 (20 和 40 mg/kg) 显着降低了支气管肺泡灌洗液 (BALF) 中的总细胞数以及 TNF - α和 IL-6 的产生。Mibefradil 还抑制 BALF 中的总蛋白浓度，减弱伊文思蓝外渗、MPO 活性和 NF- κB 在肺组织中激活。此外，还发现氟桂利嗪是一种广泛处方的抗偏头痛药，可有效抑制 T 型通道，也可保护小鼠免受肺损伤。这些数据表明，T 型钙通道抑制剂可能有益于治疗急性肺损伤。鼓励进一步研究 T 型钙通道在急性肺损伤中的重要作用。