K Channel Blocker Glibenclamide Prevents Radiation-Induced Lung Injury and Inhibits Radiation-Induced Apoptosis of Vascular Endothelial Cells by Increased Ca Influx and Subsequent PKC Activation.

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) channel is an ATP-dependent K channel with multiple subunits. The protective role of the K channel in vascular injury has been demonstrated in some published studies. In this work, we investigated the effect of K channel on RILI. Our findings confirmed that the K channel blocker glibenclamide, rather than the K 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 Ca influx and PKC activation, which were induced by glibenclamide pretreatment. In conclusion, the K channel blocker glibenclamide remitted RILI and inhibited the radiation-induced apoptosis of vascular endothelial cells by increased Ca influx and subsequent PKC activation.