Fang Ting, Li Yapei, Peng Zhouyangfan, Zhang Zhen, Chen Fengyuan
Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Pharmacy, Central South University, Changsha 410013, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Dec 28;42(12):1361-1366. doi: 10.11817/j.issn.1672-7347.2017.12.002.
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 HMGB1 plus 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.
探讨白细胞介素-1α(IL-1α)对人脐静脉内皮细胞(HUVECs)衰老及高迁移率族蛋白1(HMGB1)功能的影响。方法:将HUVECs随机分为对照组、IL-1α组(10 ng/mL IL-1α)、HMGB1组(100 ng/mL HMGB1)和HMGB1 + IL-1α组(100 ng/mL HMGB1加10 ng/mL IL-1α)。采用衰老相关β-半乳糖苷酶(SA β-gal)染色评估衰老细胞数量,进行蛋白质免疫印迹法检测沉默信息调节因子1(SIRT1)蛋白水平,采用定量实时聚合酶链反应(qRT-PCR)检测p53、p21和p16的mRNA水平。结果:与对照组相比,IL-1α组SA β-gal阳性细胞数量显著增加(P<0.05),而SIRT1蛋白表达显著降低(P<0.01)。与IL-1α组相比,HMGB1 + IL-1α组SA β-gal阳性细胞表达减少,p21和p53的mRNA水平下调(均P<0.05),然而,p16的mRNA表达无统计学意义(P>0.05)。结论:IL-1α可诱导HUVECs衰老,HMGB1可能通过p53-p21途径抑制IL-1α诱导的内皮细胞衰老。