南方医科大学学报2025，Vol.45Issue(7)：1353-1362,10.DOI:10.12122/j.issn.1673-4254.2025.07.01
热应激对大鼠胸主动脉内皮细胞生物钟基因Bmal1和细胞周期蛋白表达水平的影响
Heat stress affects expression levels of circadian clock gene Bmal1 and cyclins in rat thoracic aortic endothelial cells
摘要
Abstract
Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.关键词
热应激/生物钟基因/Bmal1/胸主动脉内皮细胞/周期蛋白/细胞凋亡Key words
heat stress/circadian clock genes/Bmal1/thoracic aortic endothelial cells/cyclins/apoptosis引用本文复制引用
常笑语,张瀚文,曹红亭,侯玲,孟鑫,陶虹,罗彦,李光华..热应激对大鼠胸主动脉内皮细胞生物钟基因Bmal1和细胞周期蛋白表达水平的影响[J].南方医科大学学报,2025,45(7):1353-1362,10.基金项目
Supported by Natural Science Foundation of Ningxia Hui Autonomous Region(No.2023AAC03218 and 2023AAC03237).宁夏自然科学基金(2023AAC03218,2023AAC03237) （No.2023AAC03218 and 2023AAC03237）
