SIRT1激动剂促进老化内皮细胞增殖和成血管能力
SIRT1 activator promotes the proliferation vascularization ability of aged endothelial cells
董丽萍 1唐枫怡 2陶俊龙 2李涵 2袁衡 3周茜2
作者信息
- 1. 长沙医学院护理学院;新型药物制剂研发湖南省重点实验室
- 2. 长沙医学院护理学院
- 3. 长沙医学院基础医学院,长沙 410219
- 折叠
摘要
目的 探讨沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog-1,SIRT1)抑制剂EX-527与激动剂SRT1720对老化内皮细胞成血管能力的影响.方法 采用体外培养大鼠原代主动脉内皮细胞衰老技术,通过培养细胞的自然倍增建立大鼠主动脉内皮细胞(rat aorta endothelial cell,RAEC)衰老的细胞模型.内皮细胞的衰老用SA-β-Gal染色进行鉴定.衰老细胞模型建立后,对衰老的RAEC分别给予SIRT1抑制剂EX527和SIRT1激动剂SRT1720干预.运用Ki-67 免疫荧光染色检测内皮细胞增殖,采用基质胶内皮管形成实验检测内皮细胞内皮管形成,应用蛋白印迹技术检测内皮细胞eNOS表达.结果 SIRT1 激动剂抑制老化RAEC增殖能力、内皮管形成能力和eNOS表达的降低,而SIRT1抑制剂使老化RAEC的增殖能力、内皮管形成能力和eNOS表达降低.结论 SIRT1促进RAEC的增殖和内皮管形成,并增强RAEC中eNOS的表达;SIRT1改善衰老内皮细胞受损的成血管能力可能与其抑制衰老RAEC eNOS表达的下调有关.
Abstract
Objective To explore the effects of the silent mating type information regulation 2 homolog-1(SIRT1)inhibitor EX-527 and activator SRT1720 on the angiogenic capacity of senescent endothelial cells.Methods Senescence of rat aorta endothelial cells(RAEC)was induced using an in vitro culture of primary RAEC,employing natural cell doubling to establish a senescent cell model.The senescence of endothelial cells was identified using SA-β-Gal staining.After establishing the senescent cell model,inter-ventions with SIRT1 inhibitor EX527 and SIRT1 activator SRT1720 were applied to the senescent RAECs.Ki-67 immunofluorescence staining was used to assess endothelial cell proliferation,matrix gel endothelial tube formation assay to evaluate the ability to form endothelial tubes,and Western blotting to detect the expression of endothelial nitric oxide synthase(eNOS)in the endothelial cells.Results The SIRT1 activator reduced the diminished proliferation capacity,endothelial tube formation,and eNOS expression in aged RAECs,whereas the SIRT1 inhibitor exacerbated the reduction in these capacities.Conclusion SIRT1 promotes the proliferation and endothelial tube formation of RAECs,and enhances eNOS expression in RAECs.The improvement of the angiogenic capacity in se-nescent endothelial cells by SIRT1 may be associated with its suppression of the downregulation of eNOS expression in aged RAECs.
关键词
大鼠主动脉内皮细胞/SIRT1/eNOSKey words
Rat aorta endothelial cell/SIRT1/eNOS引用本文复制引用
基金项目
长沙市科技局杰出创新青年培养计划(kq2305024)
湖南省教育厅重点项目(23A0668)
湖南省教育厅优秀青年项目(22B0896)
湖南省教育厅一般项目(23C0465)
湖南省大学生创新创业训练计划项目(湘教通[2023]237号)
出版年
2024
NETL
NSTL
万方数据