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.
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/mL IL-1α孵育)、HMGB1组(100 ng/mL HMGB1孵育)、HMGB1+IL-1α组(100 ng/mL HMGB1和10 ng/mL IL-1α共同孵育)，采用细胞衰老相关β-半乳糖苷酶(senescence associated β-galactosidase，SA β-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，qRT-PCR)检测衰老相关基因p53，p21和p16的mRNA表达。结果：与对照组相比，IL-1α组SA β-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SA β-gal染色阳性细胞减少，p21和p53的mRNA表达下调(均P<0.05)，但p16的mRNA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。.