[1]何春艳,裴美娟,李玉明,等.发状分裂增强子1对胆固醇刺激下内皮细胞的影响及机制研究[J].陕西医学杂志,2023,52(9):1115-1119.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.001]
　HE Chunyan,PEI Meijuan,LI Yuming,et al.Effect and mechanism of HES-1 on cholesterol stimulated endothelial cells[J].,2023,52(9):1115-1119.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.001]
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发状分裂增强子1对胆固醇刺激下内皮细胞的影响及机制研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年9期
页码:
1115-1119
栏目:
基础研究
出版日期:
2023-09-05

文章信息/Info

Title:
Effect and mechanism of HES-1 on cholesterol stimulated endothelial cells
作者:
何春艳1; 裴美娟1; 李玉明2; 王会荣3
(1.武警特色医学中心神经内科,天津 300162; 2.武警特色医学中心心血管疾病研究所,天津 300162; 3.宝鸡市人民医院神经外科,陕西 宝鸡 721000)
Author(s):
HE Chunyan; PEI Meijuan; LI Yuming; WANG Huirong
(Department of Neurology,Characteristic Medical Center of Chinese People's Armed Police Force,Tianjin 300162,China)
关键词:
动脉粥样硬化;  发状分裂增强子1;  胆固醇;  内皮细胞;  凋亡;  Wnt/PI3K/AKT/β-catenin信号通路
Keywords:
Atherosclerosis;  Hairy and enhancer of split homolog-1;  Cholesterol;  Endothelial cells;  Apoptosis;  Wnt/PI3K/AKT/β-catenin signaling pathway
分类号:
R 543.5
DOI:
DOI:10.3969/j.issn.1000-7377.2023.09.001
文献标志码:
A
摘要:
目的:探讨发状分裂增强子1(HES-1)对胆固醇刺激下内皮细胞的影响及潜在机制。方法:应用Ea.hy926细胞构建HES-1过表达细胞和HES-1基因敲除细胞。将细胞分为CH组(胆固醇刺激)、GO组(HES-1过表达+胆固醇刺激)、GD组(HES-1低表达+胆固醇刺激)和NC组(空白对照组)。采用流式细胞术检测细胞凋亡情况。采用蛋白质印迹检测凋亡相关蛋白表达水平以及无翼型MMTV家族整合位点(Wnt)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/β-连锁蛋白(β-catenin)信号通路相关蛋白表达水平。采用酶联免疫吸附法(ELISA)检测血管生成相关因子表达水平。结果:与NC组比较,所有胆固醇处理组凋亡细胞占比显著增加(均P<0.05)。与CH组比较,GO组凋亡细胞占比显著增加(P<0.05)。与NC组比较,CH组和GO组B淋巴细胞瘤-2(Bcl-2)相关X蛋白(Bax)、半胱天冬酶3(Caspase-3)、Caspase-9、p-BIM/BIM表达显著升高,Bcl-2表达显著降低(均P<0.05); GD组Bax、Caspase-9表达显著升高,Bcl-2、Caspase-3表达显著降低(均P<0.05)。与CH组比较,GO组Bax、Caspase-9表达显著升高,Bcl-2表达显著降低(均P<0.05); GD组Bax、Bcl-2、Caspase-3、Caspase-9、磷酸化Bcl-2相互作用细胞死亡介质(p-BIM)/BIM表达显著降低(均P<0.05)。与GO组比较,GD组Bax、Caspase-3、Caspase-9、p-BIM/BIM表达显著降低(均P<0.05)。与NC组比较,CH组和GO组转化生长因子-β(TGF-β)、胰岛素样生长因子(IGF)、血管内皮生长因子α(VEGF-α)、血小板衍生生长因子(PDGF)表达显著降低(均P<0.05); GD组PDGF表达显著降低(P<0.05)。与CH组比较,GO组TGF-β、IGF、VEGF-α、PDGF表达显著降低(均P<0.05); GD组TGF-β、IGF、PDGF表达显著升高(均P<0.05)。与GO组比较,GD组TGF-β、IGF、VEGF-α、PDGF表达显著升高(均P<0.05)。与NC组比较,CH组HES-1表达显著升高,p-AKT/AKT、c-myc表达显著降低(均P<0.05); GO组HES-1表达显著升高,Wnt、p-AKT/AKT、β-catenin、c-myc表达显著降低(均P<0.05); GD组HES-1、Wnt、β-catenin、c-myc表达显著降低,p-AKT/AKT显著升高(均P<0.05)。与CH组比较,GO组HES-1表达显著升高,Wnt、p-AKT/AKT、β-catenin、c-myc表达显著降低(均P<0.05); GD组HES-1、Wnt、β-catenin表达显著降低,p-AKT/AKT、c-myc表达显著升高(均P<0.05)。与GO组比较,GD组HES-1表达显著降低,Wnt、p-AKT/AKT、β-catenin、c-myc表达显著升高(均P<0.05)。结论:HES-1过表达可抑制Wnt/PI3K/AKT/β-catenin信号通路,促进细胞凋亡,抑制血管生成相关因子的表达。
Abstract:
Objective:To investigate the effect and potential mechanism of hairy and enhancer of split homolog-1(HES-1)on cholesterol stimulated endothelial cells.Methods:Ea.hy926 cells were applied to construct HES-1 overexpression cells and HES-1 knockdown cells.The cells were divided into CH group(cholesterol stimulation applied alone),GO group(HES-1 overexpression combined with cholesterol stimulation),GD group(HES-1 low expression combined with cholesterol stimulation)and NC group(blank control group).Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the expression levels of apoptosis-related proteins and the expression levels of Wnt/PI3K/AKT/β-catenin signaling pathway-related proteins.The expression levels of angiogenesis-related factors were detected by ELISA.Results:Compared with NC group,the proportion of apoptotic cells in all cholesterol treatment groups was significantly increased(all P<0.05).Compared with CH group,the proportion of apoptotic cells in GO group was significantly increased(P<0.05).Compared with NC group,the expressions of Bax,Caspase-3,Caspase-9 and p-BIM/BIM in CH group and GO group were significantly increased,and the expression of Bcl-2 was significantly decreased(all P<0.05); the expressions of Bax and Caspase-9 in GD group were significantly increased,while the expressions of Bcl-2 and Caspase-3 were significantly decreased(all P<0.05).Compared with CH group,the expressions of Bax and Caspase-9 in GO group were significantly increased,and the expression of Bcl-2 was significantly decreased(all P<0.05); the expressions of Bax,Bcl-2,Caspase-3,Caspase-9 and p-BIM/BIM in GD group were significantly decreased(all P<0.05).Compared with GO group,the expressions of Bax,Caspase-3,Caspase-9 and p-BIM/BIM in GD group were significantly decreased(all P<0.05).Compared with NC group,the expressions of TGF-β,IGF,VEGF-α and PDGF in CH group and GO group were significantly decreased(all P<0.05); the expression of PDGF in GD group was significantly decreased(P<0.05).Compared with CH group,the expressions of TGF-β,IGF,VEGF-α and PDGF in GO group were significantly decreased(all P<0.05); the expressions of TGF-β,IGF and PDGF in GD group were significantly increased(all P<0.05).Compared with GO group,the expressions of TGF-β,IGF,VEGF-α and PDGF in GD group were significantly increased(all P<0.05).Compared with NC group,the expression of HES-1 in CH group was significantly increased,and the expressions of p-AKT/AKT and c-myc were significantly decreased(all P<0.05); the expression of HES-1 in GO group was significantly increased,and the expressions of Wnt,p-AKT/AKT,β-catenin and c-myc were significantly decreased(all P<0.05); the expressions of HES-1,Wnt,β-catenin and c-myc in GD group were significantly decreased,and p-AKT/AKT was significantly increased(all P<0.05).Compared with CH group,the expression of HES-1 was significantly increased,and the expressions of Wnt,p-AKT/AKT,β-catenin and c-myc were significantly decreased in GO group(all P<0.05); the expressions of HES-1,Wnt and β-catenin in GD group were significantly decreased,and the expressions of p-AKT/AKT and c-myc were significantly increased(all P<0.05).Compared with GO group,the expression of HES-1 in GD group was significantly decreased,while the expressions of Wnt,p-AKT/AKT,β-catenin and c-myc were significantly increased(all P<0.05).Conclusion:Overexpression of HES-1 can inhibit Wnt/PI3K/AKT/β-catenin signaling pathway,promote cell apoptosis,and inhibit the expression of angiogenesis-related factors.

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备注/Memo

备注/Memo:
基金项目:国家重点研发计划项目(2017YFC1307602)
更新日期/Last Update: 2023-09-04