HAO Xiaohui),ZHAO Mingzhong),ZHANG Yuzhi),et al.Effects of overexpression of cellular repressor of E1A-stimulated gene on vascular endothelial cell injury induced by OxLDL[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2019,(02):258-262.[doi:10.13705/j.issn.1671-6825.2018.08.110]





Effects of overexpression of cellular repressor of E1A-stimulated gene on vascular endothelial cell injury induced by OxLDL
1)郑州市第九人民医院心脏中心 郑州 450053 2)阜外华中心血管病医院心内科 郑州 450000
HAO Xiaohui1) ZHAO Mingzhong1) ZHANG Yuzhi1) ZHANG Zufeng1) ZHU Qiuping1)NIU Fangqing2)
1)Heart Center,the Ninth People's Hospital of Zhengzhou, Zhengzhou 450053 2)Department of Cardiology,Fuwai Central China Cardiovascular Hospital,Zhengzhou 450000
血管内皮细胞 凋亡 E1A激活基因阻遏子 OxLDL
vascular endothelial cell apoptosis cellular repressor of E1A-stimulated gene OxLDL
目的:研究过表达E1A激活基因阻遏子(CREG)对氧化低密度脂蛋白(OxLDL)诱导的血管内皮细胞损伤的影响。方法:血管内皮细胞分为4组,空白对照组不处理; OxLDL组用100 mg/L OxLDL处理24 h; 另2组分别感染对照逆转录病毒(阴性对照组)和pLNCX-CREG重组逆转录病毒(pLNCX-CREG组),之后均用100 mg/L OxLDL处理24 h。用Real-time PCR和Western blot法检测4组细胞CREG mRNA和蛋白的表达,用硫代巴比妥酸法检测培养液中丙二醛(MDA)含量,黄嘌呤氧化酶法检测培养液中超氧化物歧化酶(SOD)活性,DCFH-DA法检测培养液中活性氧(ROS)水平,流式细胞术检测细胞凋亡,Western blot法检测细胞中活化的Caspase-3(Cleaved Caspase-3)蛋白的表达水平。结果:与空白对照组比较,OxLDL组细胞中CREG mRNA和蛋白表达水平均降低; pLNCX-CREG组细胞中CREG mRNA和蛋白表达水平均较OxLDL组升高(P<0.05)。与空白对照组比较,OxLDL组细胞SOD活性降低,MDA和ROS水平升高,细胞凋亡率和Cleaved Caspase-3蛋白表达水平均升高; 与OxLDL组比较,pLNCX-CREG组细胞氧化损伤指标的变化被逆转,细胞凋亡率及Cleaved Caspase-3蛋白表达水平均降低(P<0.05)。结论:过表达CREG可以抑制OxLDL诱导的血管内皮细胞氧化损伤并抑制细胞凋亡。
Aim:To study the effects of cellular repressor of E1A-stimulated gene(CREG)overexpression on vascular endothelial cell injury induced by OxLDL.Methods:Vascular endothelial cells were divided into four groups, the blank control group was not treated, the OxLDL group was treated with 100 mg/L OxLDL for 24 hours, the other two groups were infected with control retrovirus(negative control group)and pLNCX-CREG retrovirus(pLNCX-CREG group), and then treated with 100 mg/L OxLDL for 24 hours. The expression of CREG was detected by Real-time PCR and Western blot. The content of malondialdehyde(MDA)in culture fluid was detected by thiobarbituric acid, the activity of superoxide dismutase(SOD)was detected by xanthine oxidase,and the level of reactive oxygen species(ROS)was detected by DCFH-DA.The apoptosis was detected by flow cytometry, and the activated Caspase-3(Cleaved Caspase-3)was detected by Western blot.Results:Compared with the blank control group, the expression levels of CREG mRNA and protein in the OxLDL group were decreased, while those in the pLNCX-CREG group were increased compared with the OxLDL group(P<0.05). Compared with the blank control group, SOD activity decreased, MDA and ROS levels increased, apoptotic rate and Cleaved Caspase-3 protein expression increased in the OxLDL group. Compared with the OxLDL group, the changes of oxidative damage indexes in the pLNCX-CREG group were reversed, apoptotic rate and expression of Cleaved Caspase-3 protein were decreased(P<0.05).Conclusion:Overexpression of CREG can inhibit oxidative damage and reduce apoptosis of vascular endothelial cells induced by OxLDL.


[1] WU GC,LIU HR,LENG RX,et al.Subclinical atherosclerosis in patients with systemic lupus erythematosus:a systemic review and meta-analysis[J].Autoimmun Rev,2016,15(1):22
[2] CHANG MC,LEE JJ,CHEN YJ,et al.Lysophosphatidylcholine induces cytotoxicity/apoptosis and IL-8 production of human endothelial cells:Related mechanisms[J].Oncotarget,2017,8(63):106177
[3] 华婷,张妍,王昕,等.E1A激活基因阻遏子抑制细胞凋亡机制的研究进展[J].中国实用眼科杂志,2016,34(3):206
[4] WANG N,HAN YL,TAO J,et al.Overexpression of CREG attenuates atherosclerotic endothelium apoptosis via VEGF/PI3K/AKT pathway[J].Atherosclerosis,2011,218(2):543
[5] 刘艳霞,闫承慧,田孝祥,等.CREG基因启动子区甲基化调控在动脉粥样硬化发生中的机制研究[J].中国循环杂志,2016,31(z1):18
[6] 王娜,韩雅玲,陶杰,等.p38MAPK介导E1A激活基因阻遏子蛋白调控人血管内皮细胞凋亡[J].中国病理生理杂志,2011,27(7):1329
[7] TSAI KL,HUNG CH,CHAN SH,et al.Baicalein protects against oxLDL-caused oxidative stress and inflammation by modulation of AMPK-alpha[J].Oncotarget,2016,7(45):72458
[8] TENG W,QIU C,HE Z,et al.Linc00152 suppresses apoptosis and promotes migration by sponging miR-4767 in vascular endothelial cells[J].Oncotarget,2017,8(49):85014
[9] TORISU K,SINGH KK,TORISU T,et al.Intact endothelial autophagy is required to maintain vascular lipid homeostasis[J].Aging Cell,2016,15(1):187
[10]HINDER LM,O'BRIEN PD,HAYES JM,et al.Dietary reversal of neuropathy in a murine model of prediabetes and metabolic syndrome[J].Dis Model Mech,2017,10(6):717
[11]LOPES-VIRELLA MF,HUNT KJ,BAKER NL,et al.High levels of AGE-LDL, and of IgG antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL in circulating immune complexes predict macroalbuminuria in patients with type 2 diabetes[J].J Diabetes Complications,2016,30(4):693
[12]MONDAL NK,ROYCHOUDHURY S,MUKHERJEE S,et al.Increased risk of cardiovascular disease in premenopausal female ragpickers of Eastern India: involvement of inflammation, oxidative stress, and platelet hyperactivity[J].Mol Cell Biochem,2016,419(1/2):193
[13]ZHOU F,LIU D,NING HF,et al.The roles of p62/SQSTM1 on regulation of matrix metalloproteinase-9 gene expression in response to oxLDL in atherosclerosis[J].Biochem Biophys Res Commun,2016,472(3):451
[14]DU L,MA L,QI F,et al.Characterization of a unique pathway for 4-cresol catabolism initiated by phosphorylation in corynebacterium glutamicum[J].J Biol Chem,2016,291(12):6583
[15]LIU J,QI Y,LI S,et al.CREG1 interacts with Sec8 to promote cardiomyogenic differentiation and cell-cell adhesion[J].Stem Cells,2016,34(11):2648
[16]KURTZ A,SELTMANN S,BAIROCH A,et al.A standard nomenclature for referencing and authentication of pluripotent stem cells[J].Stem Cell Reports,2018,10(1):1
[19]QI J,ZHENG JB,AI WT,et al.Felodipine inhibits ox-LDL-induced reactive oxygen species production and inflammation in human umbilical vein endothelial cells[J].Mol Med Rep,2017,16(4):4871
[20]KALEEM S,SIDDIQUI S,SIDDIQUI HH,et al.Eupalitin induces apoptosis in prostate carcinoma cells through ROS generation and increase of caspase-3 activity[J].Cell Biol Int,2016,40(2):196
[21]SHIM JH,GIM H,LEE S,et al.Inductions of Caspase-, MAPK- and ROS-dependent apoptosis and chemotherapeutic effects caused by an ethanol extract of scutellaria barbata D.Don in human gastric adenocarcinoma cells[J].J Pharmacopuncture,2016,19(2):129


 CHAO Weijing),LI Kanghua),DAI Rongping),et al.Differentiation of human adipose derivedmesenchymal stem cells into cells of retina in vitro[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(02):407.
 ZHAO Baoming,LI Fengliang,SONG Ximing.Influence of reduced glutathione on prostacyclin and endothelin1 secretion of human umbilical vein endothelial cells cultured with AGE[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2011,(02):599.
 LIANG Ruiying),ZHAO Yue),XU Yanli),et al.Influence of casting cobalt chromium alloy Ag-containing coating on L929 cell proliferation and apoptosis[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2013,(02):803.
[4]阙菡雅),王小龙),李 杰),等.沉默热休克蛋白70基因对A549细胞凋亡的影响[J].郑州大学学报(医学版),2015,(05):641.
 QUE Hanya),WANG Xiaolong),LI Jie),et al.Effect of silencing HSP70 gene on apoptosis of A549 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2015,(02):641.
 XU Xiaoyan),WANG Xiaowei),QUE Hanya),et al.Effect of silencing NOX1 on proliferation of A549 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):330.
[6]罗 源),王春美),朱相展),等.虎杖苷对K562细胞增殖及凋亡的影响[J].郑州大学学报(医学版),2016,(03):389.
 LUO Yuan),WANG Chunmei),ZHU Xiangzhan),et al.Effect of polydatin on cell proliferation and apoptosis of leukemia cell line K562[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):389.
[7]朱相展),张彦婷),杨 露),等.β-胡萝卜素对食管鳞癌EC1细胞增殖、凋亡、迁移及细胞周期的影响[J].郑州大学学报(医学版),2016,(04):437.
 ZHU Xiangzhan),ZHANG Yanting),YANG Lu),et al.Effects of β-carotene on proliferation, apoptosis, migration and cell cycle of EC1 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):437.
 LANG Lixiang,XIN Yaping,FENG Shuhuan,et al.Detection of expressions of GRP78,TRAF2,and Caspase-12 in pancreatic tissue of gestational diabetes mellitus rats[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):458.
[9]张 妍,史占江,牛春玲,等.丹蒌片对同型半胱氨酸诱导的兔主动脉内皮细胞CHOP、BIP蛋白表达和凋亡的影响[J].郑州大学学报(医学版),2016,(04):463.
 ZHANG Yan,SHI Zhanjiang,NIU Chunling,et al.Effect of Danlou tablet on CHOP,BIP protein expressions and apoptosis of rabbit aortic endothelial cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):463.
[10]张壮丽)△,赵 宁),王亚飞),等.鱼腥草挥发油对Raji细胞增殖和凋亡的影响[J].郑州大学学报(医学版),2016,(04):474.
 ZHANG Zhuangli),ZHAO Ning),WANG Yafei),et al.Effect of volatile oil from houttuyniae herba on proliferation and apoptosis of Raji cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(02):474.


更新日期/Last Update: 2019-03-20