Department of Anesthesiology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, 310012, Zhejiang, China.
Hum Cell. 2018 Jan;31(1):64-71. doi: 10.1007/s13577-017-0184-8. Epub 2017 Oct 11.
Midazolam is a sedative used by patients with mechanical ventilation. However, the potential clinical value is not fully explored. In this report, we made use of a neuroblastoma-spinal cord hybrid motor neuron-like cell line NSC34, and elucidated the potential role of Midazolam on these cells under the insult of oxidative stress. We found the protective effect of Midazolam on motor neurons against cytotoxicity induced by the combination of oligomycin A and rotenone (O/R) or phenylarsine oxide. The characteristics of apoptosis, such as the ratio of TUNEL+ cells or the expression level of cleaved Caspase-3, was decreased by 22 or 45% in the presence of Midazolam. Furthermore, this effect was correlated with the JNK-ERK signaling pathway. Either phosphorylation of ERK or JNK was positively or negatively modulated with the treatment of Midazolam in NSC34 cells attacked by reactive oxygen species. Meanwhile, inhibition or activation of the JNK-ERK pathway regulated the protective effect of Midazolam on NSC34 cells with oxidative stress insult. Collectively, this study elucidated a previously unidentified clinical effect of Midazolam, and put forward the great promise that Midazolam may be considered as a potential candidate to the treatment of motor neuron disease.
咪达唑仑是一种镇静剂，用于机械通气患者。然而，其潜在的临床价值尚未得到充分探索。在本报告中，我们利用一种神经母细胞瘤-脊髓混合运动神经元样细胞系 NSC34，阐明了咪达唑仑在氧化应激下对这些细胞的潜在作用。我们发现咪达唑仑对运动神经元具有保护作用，可抵抗寡霉素 A 和鱼藤酮（O/R）或苯胂氧化物联合诱导的细胞毒性。在存在咪达唑仑的情况下，凋亡的特征，如 TUNEL+细胞的比例或 cleaved Caspase-3 的表达水平，降低了 22%或 45%。此外，这种作用与 JNK-ERK 信号通路有关。在被活性氧攻击的 NSC34 细胞中，咪达唑仑的处理分别正向或负向调节 ERK 或 JNK 的磷酸化。同时，JNK-ERK 通路的抑制或激活调节了咪达唑仑对氧化应激损伤的 NSC34 细胞的保护作用。总的来说，这项研究阐明了咪达唑仑以前未被识别的临床作用，并提出了一个很大的希望，即咪达唑仑可能被认为是治疗运动神经元疾病的潜在候选药物。
