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Multiple exposures to low-dose ionizing radiation induced the initiation and progression of pro-atherosclerotic phenotypes in mice and vascular endothelial cell damage
Science Progress ( IF 2.1 ) Pub Date : 2024-02-22 , DOI: 10.1177/00368504241228668
Meng-Meng Liu 1 , Chun-Yan Ding 1, 2 , Zhi-Hui Li 3 , Ru-Han Yi 1 , Li-Ping Ma 1 , Xiang-Ming Ou 1 , Hai-Xiang Liu 1 , Ling Gao 1 , Qing-Jie Liu 1
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ObjectiveThis study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells.MethodsWild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43.ResultsHematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure.ConclusionRepeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.

中文翻译:

多次暴露于低剂量电离辐射可诱导小鼠促动脉粥样硬化表型的发生和进展以及血管内皮细胞损伤

目的探讨低剂量辐射对小鼠腹主动脉及血管内皮细胞的影响。方法野生型和荷瘤小鼠接受15次低剂量辐射,累积辐射剂量为187.5, 375 和 750 毫戈瑞。评估了对心血管系统的影响。免疫组织化学分析了腹主动脉中 PAPP-A、CD62、P65 和 COX-2 的蛋白表达。微阵列技术、基因本体分析和通路富集分析评估了暴露于 375 mGy X 射线的内皮细胞的基因表达变化。使用细胞计数试剂盒 8 测定法评估细胞活力。免疫荧光染色测量 γ-H2AX 水平,实时聚合酶链反应定量白细胞介素 6 (IL-6)、ICAM-1 和 Cx43 的 mRNA 水平。结果苏木精和伊红染色显示内膜增厚,平滑肌排列不规则。在 375 和 750 mGy 下,中膜中的肌肉细胞。在 750 mGy 的照射下,观察到内膜出现炎症,荷瘤小鼠的心脏出现明显的炎症反应。免疫组织化学表明,照射后 PAPP-A、P65 和 COX-2 水平升高。微阵列分析显示 425 个上调基因和 235 个下调基因与内皮细胞间粘附、IL-6 和 NF-κB 信号传导等过程相关。Cell Counting Kit 8 检测结果表明 EA.hy926 细胞在 750 mGy 下活力受到抑制。免疫荧光染色显示 γ-H2AX 病灶呈剂量依赖性增加。逆转录定量 PCR 结果显示 750 mGy X 射线照射后 EA.hy926 细胞中 IL6、ICAM-1 和 Cx43 的表达增加。结论重复低剂量电离辐射照射引发小鼠促动脉粥样硬化表型的发展并损害血管内皮细胞。
更新日期:2024-02-22
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