高迁移率族蛋白B1在IL-1α诱导的内皮细胞衰老过程中的作用  

Role of high mobility group protein B1 in IL-1α-induced endothelial cell senescence

作　　者：方婷 李亚培[1] 彭舟扬帆 张震[3] 陈丰原[1,3] 

机构地区：[1]中南大学湘雅三医院心内科,长沙410013 [2]中南大学药学院,长沙410013 [3]中南大学血管疾病转化医学中心,长沙410013

出　　处：《中南大学学报（医学版）》2017年第12期1361-1366,共6页Journal of Central South University ：Medical Science

基　　金：国家重点基础研究发展计划(973计划)(2014CB542400);国家自然科学基金(91339204;91639301;81370253)~~

摘　　要：目的:探讨炎症因子白介素-1α(interleukin-1α,IL-1α)对人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)衰老的影响,并探讨高迁移率族蛋白B1(high mobility group protein B1,HMGB1)在其中的作用及机制。方法:将HUVECs随机分为对照组(不加处理)、IL-1α组(10 ng/m L IL-1α孵育)、HMGB1组(100 ng/m L HMGB1孵育)、HMGB1+IL-1α组(100 ng/m L HMGB1和10 ng/m L IL-1α共同孵育),采用细胞衰老相关β-半乳糖苷酶(senescence associatedβ-galactosidase,SAβ-gal)染色检测细胞衰老数目,采用Western印迹检测沉默信息调节子1(silent information regulator 1,SIRT1)的蛋白表达,采用实时荧光定量PCR(quantitative real-time PCR,q RT-PCR)检测衰老相关基因p53,p21和p16的m RNA表达。结果:与对照组相比,IL-1α组SAβ-gal染色阳性细胞数目明显增加(P<0.05),SIRT1蛋白表达水平明显下调(P<0.01)。与IL-1α组相比,HMGB1+IL-1α组SAβ-gal染色阳性细胞减少,p21和p53的m RNA表达下调(均P<0.05),但p16的m RNA表达差异无统计学意义(P>0.05)。结论:IL-1α能诱导血管内皮细胞的衰老,其中HMGB1可能通过p53-p21途径抑制IL-1α诱导的内皮细胞衰老过程。Objective： To explore the effect of interleukin-1α（IL-1α） on the senescence of human umbilical vein endothelial cells（HUVECs） and the function of high mobility group protein 1（HMGB1）.Methods： HUVECs were randomly divided into a control group, a IL-1α group（10 ng/mL IL-1α）,a HMGB1 group（100 ng/mL HMGB1）, and a HMGB1＋IL-1α group（100 ng/mL of HMGB1plus 10 ng/mL of IL-1α）. Senescence associated β-galactosidase（SA β-gal） staining was used to assess the number of senescent cells, Western blot were performed to detect the protein levels of silent information regulator 1（SIRT1）, and quantitative real-time PCR（qRT-PCR） was used to detect the mRNA levels of p53, p21 and p16.Results： Compared with the control group, the number of SA β-gal positive cells were significantly increased in the IL-1α group（P〈0.05）, while the expression of SIRT1 protein significantly decreased（P〈0.01）. Compared with the IL-1α group, the expression of SA β-gal positive cells in the HMGB1＋IL-1α group was decreased and the mRNA levels of p21 and p53 were down-regulated（all P〈0.05）, however, there was no statistical significance in the mRNA expression of p16（P〈0.05）.Conclusion： IL-1α can induce the senescence of HUVECs, and HMGB1 may inhibit IL-1α-induced endothelial cell senescence via p53-p21 pathway.

关 键 词：血管内皮细胞 衰老 炎症 IL-1Α 高迁移率族蛋白1 

分 类 号：R54[医药卫生—心血管疾病]