The Department of Neurology, Affiliated Hospital of Jianghan University, Wuhan 430015, Hubei Province, China , 13476028179@163.com
Abstract: (15 Views)
Background:This study aimed to investigate the regulatory mechanisms of brain microvascular endothelial cell (BMEC) permeability, with a focus on the role of Kir2.1 (KCNJ2) potassium channels and their potential interaction with ionizing radiation (IR). Materials and Methods: BMECs were isolated from seven-day-old Sprague-Dawley rats, and cells were stimulated with lipopolysaccharide (LPS) to evaluate inflammatory responses. A 6-MV linear accelerator was used to deliver single radiation doses (0–8 Gy) to confluent BMEC monolayers to simulate clinical radiotherapy conditions. RhoA activity, p115RhoGEF expression, and tight junction (TJ) proteins (ZO-1, occludin, claudin-5) were detected by Western blotting. Transendothelial electrical resistance (TEER) was used to assess changes in barrier permeability. Results: LPS stimulation significantly increased p115RhoGEF expression at 1, 3, and 6 h compared with the control (P<0.05). TEER values decreased progressively after LPS exposure, indicating impaired barrier integrity (P<0.05). Claudin-5 levels showed no significant change, whereas ZO-1 and occludin were markedly reduced at 6 h and 12 h (P<0.05). Radiation exposure produced similar permeability-enhancing effects, supporting shared mechanisms of barrier disruption. Conclusion: LPS-induced inflammation increases BMEC permeability primarily through downregulation of TJ proteins. Ionizing radiation produces comparable barrier-disruptive effects, suggesting overlapping regulatory pathways. These findings support a potential role for Kir2.1 channels in modulating BMEC permeability under both inflammatory and radiation-induced stress.