普萘洛尔对人脐静脉内皮细胞生物学行为及SOX18、MMP-7、VEGFA表达的影响

Effects of propranolol on the biological behavior of human umbilical vein endothelial cells and the expression of SOX18, MMP-7, and VEGFA

摘要:

目的 探讨普萘洛尔对人脐静脉内皮细胞（human umbilical vein endothelial cell, HUVEC）增殖、凋亡、迁移及成管能力，以及对性别决定区Y框18（sex determining region Y-box 18, SOX18）、基质金属蛋白酶-7（matrix metalloproteinase-7, MMP-7）和血管内皮生长因子A（vascular endothelial growth factor A, VEGFA）表达的影响。方法 以不同浓度的普萘洛尔处理HUVEC，采用CCK-8法检测细胞活力，选出最佳浓度及时间。实验分为对照组，普萘洛尔不同浓度（50、100、150 μmol/L）组，采用流式细胞术、细胞划痕实验和成管实验观察HUVEC凋亡、迁移和管腔形成情况，Western blot和实时荧光定量PCR法检测SOX18、MMP-7、VEGFA蛋白及mRNA表达水平。结果 与对照组相比，普萘洛尔不同浓度组细胞凋亡率升高（P<0.05），且随药物浓度增加显著升高（P<0.05）；普萘洛尔不同浓度组伤口愈合率降低，成管节点数和成管总长度减少，SOX18、MMP-7、VEGFA蛋白及mRNA表达下调（P<0.05）。结论 普萘洛尔可抑制HUVEC的增殖、迁移、成管能力并促进细胞凋亡，降低SOX18、MMP-7和VEGFA表达水平。

Abstract:

Objective To investigate the effects of propranolol on the proliferation, apoptosis, migration, and tube formation ability of human umbilical vein endothelial cells (HUVEC), as well as its impact on the expression of sex-determining region Y-box 18 (SOX18), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor A (VEGFA).Methods HUVEC were treated with different concentrations of propranolol, and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration. The experiment consisted of a control group and groups treated with different concentrations of propranolol (50, 100, 150 μmol/L). Apoptosis, migration, and tube formation of HUVEC were observed using flow cytometry, wound healing assays, and tube formation assays. Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA.Results Compared to the control group, the apoptosis rate in the propranolol treatment groups increased significantly (P<0.05), and it rose significantly with increasing drug concentration (P<0.05). The wound healing rate decreased in the propranolol treatment groups, and both the number of tube formation nodes and total tube length were reduced (P<0.05). The expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups (P<0.05).Conclusions Propranolol can inhibit the proliferation, migration, and tube formation ability of HUVEC and promote cell apoptosis, resulting in decreased expression levels of SOX18, MMP-7, and VEGFA.