Fibulin-1上调P16、P21和P53促进血管平滑肌细胞衰老的研究

doi:10.3969/j.issn.1003-9198.2026.04.006

摘要/Abstract

摘要： 目的探讨Fibulin-1对血管平滑肌细胞(VSMC)衰老的影响及其可能机制。方法体外培养的大鼠VSMC,分为3组进行实验,对照组为不含D-半乳糖的DMEM培养液,D-半乳糖组为含D-半乳糖的DMEM培养液,实验组为Fibulin-1重组蛋白+D-半乳糖的DMEM培养液。采用β-半乳糖苷酶染色分析各组间细胞衰老情况,透射电镜观察细胞超微结构变化,Western blot法检测P16、P21和P53蛋白表达。结果 β-半乳糖苷酶染色分析发现,D-半乳糖组和实验组衰老细胞数较对照组明显增多,且实验组高于D-半乳糖组(P＜0.05)。通过透射电镜观察发现,实验组细胞的细胞核及核外细胞器均呈现更加明显的衰老改变。Western blot检测显示,D-半乳糖组和实验组的P16、P21和P53蛋白表达均较对照组增高,且实验组较D-半乳糖组增高更加显著(P＜0.05)。结论 Fibulin-1重组蛋白促进VSMC细胞及亚细胞水平的衰老征象,其机制可能与Fibulin-1上调细胞周期抑制蛋白P16、P21和P53的表达有关。

关键词: Fibulin-1, 血管平滑肌细胞, 衰老, P16, P21, P53

Abstract: Objective To explore the effect of Fibulin-1 on the senescence of vascular smooth muscle cells (VSMC) and its possible mechanisms. Methods VSMCs of rat cultured in vitro were divided into three groups for the experiment. The control group was DMEM culture medium without D-galactose, the D-galactose group was DMEM culture medium containing D-galactose, and the experimental group was DMEM culture medium with Fibulin-1 recombinant protein and D-galactose. β-galactosidase staining was used to analyze the cell senescence among each group, transmission electron microscopy was used to observe the ultrastructural changes of cells, and Western blot method was used to detect the protein expressions of P16, P21 and P53. Results β-galactosidase staining analysis showed that the number of senescent cells in the D-galactose group and the experimental group was significantly increased compared with the control group, especially in the expermental group(P<0.05). Through the transmission electron microscopy, we found that the nuclei and extranuclear organelles of the cells in the experimental group showed more obvious senescence changes. The expressions of P16, P21 and P53 proteins in the D-galactose group and the experimental group were significantly increased than those in the control group, especially in the experimental group (P<0.05). Conclusions The Fibulin-1 recombinant protein promotes the aging signs of VSMC at both cellular and sub-cellular levels, and its mechanism may be related to Fibulin-1 upregulating the expressions of cell cycle inhibitory proteins P16, P21 and P53.

Key words: Fibulin-1, vascular smooth muscle cells, senescence, P16, P21, P53

中图分类号:

R 329.2

黄荣, 侯继文, 蒋华, 张丹, 汪子凯. Fibulin-1上调P16、P21和P53促进血管平滑肌细胞衰老的研究[J]. 实用老年医学, 2026, 40(4): 357-361.

HUANG Rong, HOU Jiwen, JIANG Hua, ZHANG Dan, WANG Zikai. Study on Fibulin-1 upregulating P16, P21, and P53 to promote VSMC senescence[J]. Practical Geriatrics, 2026, 40(4): 357-361.

参考文献

[1] DING Y N, TANG X, CHEN H Z, et al. Epigenetic regulation of vascular aging and age-related vascular diseases[J]. Adv Exp Med Biol, 2018, 1086:55-75.
[2] CHILDS B G, GLUSCEVIC M, BAKER D J, et al. Senescent cells:an emerging target for diseases of ageing[J]. Nat Rev Drug Discov, 2017, 16(10):718-735.
[3] TIAN X L, LI Y. Endothelial cell senescence and age-related vascular diseases[J]. J Genet Genomics, 2014, 41(9):485-495.
[4] PALOMBO C, KOZAKOVA M. Arterial stiffness, atherosclerosis and cardiovascular risk:pathophysiologic mechanisms and emerging clinical indications[J]. Vascul Pharmacol, 2016, 77:1-7.
[5] BASATEMUR G L, JØRGENSEN H F, CLARKE M C H, et al. Vascular smooth muscle cells in atherosclerosis[J]. Nat Rev Cardiol, 2019, 16(12):727-744.
[6] MIANO J M, FISHER E A, MAJESKY M W. Fate and state of vascular smooth muscle cells in atherosclerosis[J]. Circulation, 2021, 143(21):2110-2116.
[7] HANSEN M L, RASMUSSEN L M. Associations between plasma fibulin-1, pulse wave velocity and diabetes in patients with coronary heart disease[J]. J Diabetes Complications, 2015, 29(3):362-366.
[8] ARGRAVES W S, GREENE L M, COOLEY M A, et al. Fibulins:physiological and disease perspectives[J]. EMBO Rep, 2003, 4(12):1127-1131.
[9] 梁小璐, 晏丹, 罗曼蒂, 等. 腓骨蛋白-1在血管平滑肌细胞衰老相关钙化中的作用及机制研究[J]. 中华老年医学杂志, 2022, 41(5):580-585.
[10] WEI W, JI S. Cellular senescence:molecular mechanisms and pathogenicity[J]. J Cell Physiol, 2018, 233(12):9121-9135.
[11] TWAL W O, HAMMAD S M, GUFFY S L, et al. A novel intracellular fibulin-1D variant binds to the cytoplasmic domain of integrin beta 1 subunit[J]. Matrix Biol, 2015, 43:97-108.
[12] ARGRAVES W S, COOLEY M A, HARIKISHNAN K, et al. Fibulin-1 is a matricellular regulator of the RAS/mitogen activated protein kinase (MAPK)-mediated signal transduction pathway[J]. FASEB J, 2009, 23(S1):309.1.
[13] AZMAN K F, ZAKARIA R. D-Galactose-induced accelerated aging model:an overview[J]. Biogerontology, 2019, 20(6):763-782.
[14] JEYAPALAN J C, SEDIVY J M. Cellular senescence and organismal aging[J]. Mech Ageing Dev, 2008, 129(7/8):467-474.

[1]	柳雯, 刘昱廷, 纪木火. T细胞线粒体功能障碍与老年胸科手术患者术后谵妄的相关性[J]. 实用老年医学, 2026, 40(4): 382-388.
[2]	肾上腺衰老专家共识组成员, 中国康复医学会老年医学分会. 中国肾上腺衰老诊疗专家共识(2025版)[J]. 实用老年医学, 2026, 40(4): 433-444.
[3]	陈徐冠, 夏玉东, 王璎瑛, 徐云凡, 吴军. 基于单细胞多组学分析的巨噬细胞衰老在动脉粥样硬化中的作用机制研究[J]. 实用老年医学, 2026, 40(3): 241-246.
[4]	姚子童, 党小宇, 范浩玲, 朱相瑜, 黄菁菁, 冯旰珠. 老年呼吸道病毒感染合并血液系统紊乱研究进展[J]. 实用老年医学, 2026, 40(2): 206-210.
[5]	李红, 李树斌, 邬倩, 殷亚宁, 孙于欣, 格日乐其其格, 李卫红, 张士琦, 邬真力. 乙酰化调控机制在血管衰老中的研究进展[J]. 实用老年医学, 2026, 40(1): 72-77.
[6]	闫璐, 段宇. 老年糖尿病病人认知衰弱的血液生物标志物研究进展[J]. 实用老年医学, 2025, 39(9): 942-946.
[7]	姚远, 杨勇. 免疫衰老在老年非小细胞肺癌中的作用机制研究进展[J]. 实用老年医学, 2025, 39(9): 947-951.
[8]	陈佳宇, 任斌辉. 衰老相关的肿瘤转移机制研究进展[J]. 实用老年医学, 2025, 39(8): 851-856.
[9]	陈梦琪, 范浩玲, 章媛媛, 吴婷玉, 张冬梅, 程凯. 早期限时喂养模式对代谢综合征病人代谢状况及衰老相关分泌表型的影响[J]. 实用老年医学, 2025, 39(7): 669-673.
[10]	邓超维, 刘丹丽, 叶旭军. 慢性低度炎症与听力障碍的研究进展[J]. 实用老年医学, 2025, 39(6): 551-554.
[11]	刘舒. 认知储备影响认知功能的研究进展[J]. 实用老年医学, 2025, 39(3): 308-311.
[12]	马晓婷, 刘善雯, 姚琳琳, 包润莹, 李奕枫, 杨伊凡, 胡华. 炎性衰老在阿尔茨海默病疾病进程中的机制研究进展[J]. 实用老年医学, 2025, 39(2): 202-206.
[13]	赵淑晴, 赵莹, 张宇, 卢笑晖. 细胞衰老在慢性心力衰竭中的作用机制研究进展[J]. 实用老年医学, 2025, 39(1): 93-97.
[14]	仇小敏, 张伟三. 口腔衰弱与认知障碍关系的研究进展[J]. 实用老年医学, 2024, 38(9): 880-883.
[15]	孙泽东, 任斌辉. 衰老积累的表观遗传学改变与肿瘤的发生发展[J]. 实用老年医学, 2024, 38(9): 953-957.