KATP Channel Blocker Glibenclamide Prevents Radiation-Induced Lung Injury and Inhibits Radiation-Induced Apoptosis of Vascular Endothelial Cells by Increased Ca2+ Influx and Subsequent PKC Activation
KATP Channel Blocker Glibenclamide Prevents Radiation-Induced Lung Injury and Inhibits Radiation-Induced Apoptosis of Vascular Endothelial Cells by Increased Ca2+ Influx and Subsequent PKC Activation
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DOI：
10.1667/rr15381.1
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发表时间：
2020-02-01
影响因子：
3.4
通讯作者：
Liu, Hu
中科院分区：
文献类型：
--
作者：
Xia, Penglin;Cao, Kun;Liu, Hu
放射性肺损伤（RILI）是胸部放疗常见且严重的副作用，会影响患者的生活质量。最近的研究表明，早期血管损伤，尤其是微血管损伤，在 RILI 的发展中发挥着核心作用。因此，早期血管保护对于 RILI 治疗至关重要。 ATP 敏感 K+ (K-ATP) 通道是具有多个亚基的 ATP 依赖性 K+ 通道。 K-ATP 通道在血管损伤中的保护作用已在一些已发表的研究中得到证实。在这项工作中，我们研究了 K-ATP 通道对 RILI 的影响。我们的研究结果证实，K-ATP 通道阻滞剂格列本脲，而不是 K(ATP ) 通道开放剂吡那地尔，可以缓解 RILI，特别是可以针对辐射引起的血管损伤提供保护。细胞学实验证实，格列本脲可增强细胞活力，增加辐射后增殖的潜力，并减弱辐射诱导的细胞凋亡。涉及的机制包括格列本脲预处理诱导的 Ca2+ 流入增加和 PKC 激活。总之，K-ATP 通道阻滞剂格列本脲可通过增加 Ca2+ 内流和随后的 PKC 激活来缓解 RILI，并抑制辐射诱导的血管内皮细胞凋亡。 (C) 2020 年放射线研究会
Radiation-induced lung injury (RILI) is a common and severe side effect of thoracic radiotherapy, which compromises patients' quality of life. Recent studies revealed that early vascular injury, especially microvascular damage, played a central role in the development of RILI. For this reason, early vascular protection is essential for RILI therapy. The ATP-sensitive K+ (K-ATP) channel is an ATP-dependent K+ channel with multiple subunits. The protective role of the K-ATP channel in vascular injury has been demonstrated in some published studies. In this work, we investigated the effect of K-ATP channel on RILI. Our findings confirmed that the K-ATP channel blocker glibenclamide, rather than the K(ATP )channel opener pinacidil, remitted RILI, and in particular, provided protection against radiation-induced vascular injury. Cytology experiments verified that glibenclamide enhanced cell viability, increased the potential of proliferation after irradiation and attenuated radiation-induced apoptosis. Involved mechanisms included increased Ca2+ influx and PKC activation, which were induced by glibenclamide pretreatment. In conclusion, the K-ATP channel blocker glibenclamide remitted RILI and inhibited the radiation-induced apoptosis of vascular endothelial cells by increased Ca2+ influx and subsequent PKC activation. (C) 2020 by Radiation Research Society