氧化型低密度脂蛋白诱导内皮细胞凋亡中前蛋白转化酶枯草溶菌素9与炎症因子的关系

doi:10.3969/j.issn.1004-583X.2016.04.013

临床荟萃 ›› 2016, Vol. 31 ›› Issue (4): 396-402.doi: 10.3969/j.issn.1004-583X.2016.04.013

氧化型低密度脂蛋白诱导内皮细胞凋亡中前蛋白转化酶枯草溶菌素9与炎症因子的关系

钱正瑶^{1, 2}, 李广平¹, 李娇¹, 梁雪¹, 徐昭¹, 陈艳¹, 赵辉²

1.天津医科大学第二医院心脏科,天津市心血管病离子与分子机能重点实验室,天津心脏病学研究所,天津 300211;
2.天津医院心内科,天津 300211

收稿日期:2016-01-21 出版日期:2016-04-05 发布日期:2016-04-18
通讯作者: 李广平,Email:tjcardiol@126.com

Relationship between PCSK9 and inflammation factor expression in ox-LDL-induced endothelial cells apoptosis

Qian Zhengyao^1,2, Li Guangping¹, Li Jiao¹, Liang Xue¹, Xu Zhao¹, Chen Yan¹, Zhao Hui²

1. Department of Cardiology, the Secend Hospital of Tianjin Medical University, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Tianjin 300211, China;
2. Department of Cardiology, Tianjin Hospital, Tianjin 300211, China

Received:2016-01-21 Online:2016-04-05 Published:2016-04-18
Contact: Li Guangping, Email: tjcardiol@126.com

摘要/Abstract

摘要： 目的观察氧化型低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVECs)凋亡中前蛋白转化酶枯草溶菌素9(PCSK9)与炎症因子表达的关系。方法用ox-LDL处理HUVECs 0小时、12小时、24小时、36小时、48小时,分别检测PCSK9、白细胞介素6(IL-6)、单核细胞趋化蛋白1(MCP-1)、基质金属蛋白酶9(MMP-9)、C反应蛋白(CRP) mRNA和蛋白的表达以及核因子-κB (NF-κB)核位移。Lipofectamine 2000转染PCSK9小分子干扰RNA(PCSK9 siRNA)进入HUVECs 6小时后,加入ox-LDL处理24小时,分别检测PCSK9、IL-6、MCP-1、MMP-9、CRP的表达以及NF-κB核位移。结果随着ox-LDL处理时间的增加,PCSK9、IL-6、MCP-1、MMP-9、CRP mRNA的表达上调、NF-κB的核位移明显增加,以24小时表达(核位移)最明显,随后表达(核位移)逐渐减少(P<0.05);细胞培养上清液中IL-6、MCP-1、MMP-9、CRP蛋白的浓度随着时间的推移逐渐增加,48小时达到峰值,与0小时比较,48小时增加最明显(P<0.01)。siRNA组PCSK9、IL-6、MCP-1、MMP-9、CRP mRNA和蛋白的表达以及NF-κB核位移较阴性转染组明显降低(P<0.01)。结论 PCSK9 siRNA能够抑制ox-LDL诱导的HUVECs炎症因子的表达,PCSK9可能参与了炎症反应的调节。

关键词: 前蛋白转化酶类, 脂蛋白类, LDL, 人脐静脉内皮细胞, 细胞凋亡

Abstract: Objective To investigate the relationship between proprotein convertase subtilisin/kexin type 9 (PCSK9) and inflammatory factor expression in apoptosis of human umbilical vein endothelial cells (HUVECs) induced by oxidized low density lipoprotein(ox-LDL).Methods HUVECs were incubated with ox-LDL for different times (0 h,12 h,24 h,36 h,48 h). The mRNA and protein expression of PCSK9, inter leukin 6(IL-6), monocyte chemotactic protein-1(MCP-1), matrix metalloprotein-9(MMP-9), C-reactive protein (CRP) and the nucler displacement of nucler factor-kappa B (NF-κB) were detected. The siRNA for PCSK9 was designed and synthesized,then was transfected into HUVECs by Lipofectamine 2000. After transfection for 6 h, cells were treated with ox-LDL for 24 h, the mRNA and protein expression of PCSK9, IL-6, MCP-1, MMP-9, CRP and the nucler displacement of NF-κB were detected.Results With the increase of ox-LDL processing time, the mRNA expressions of PCSK9, IL-6, MCP-1, MMP-9 and CRP were significantly higher, and the nucler displacement of NF-κB was significantly increased, especially for 24 h incubation, and the subsequent expression and the nucler displacement were gradually decreased (P<0.05). The protein concentration of IL-6, MCP-1, CRP and MMP-9 in cell culture supernatant increased gradually over time, and reached the peak at 48 h. Compared with the 0 h group, the 48 h group increased most obviously (P<0.01). The mRNA and protein expressions of PCSK9, IL-6, MCP-1, MMP-9, CRP and the nucler displacement of NF-κB in siRNA group were significantly lower than those in negative transfection group (P<0.01).Conclusion PCSK9 siRNA can inhibit inflammation factor expression in apoptosis of HUVECs induced by ox-LDL. And PCSK9 may be involved in the regulation of inflammation.

Key words: proprotein convertase, lipoproteins, LDL, human umbilical vein, endothelial cells apoptosis

中图分类号:

R345.63

R341.35

引用本文

钱正瑶, 李广平, 李娇, 梁雪, 徐昭, 陈艳, 赵辉. 氧化型低密度脂蛋白诱导内皮细胞凋亡中前蛋白转化酶枯草溶菌素9与炎症因子的关系[J]. 临床荟萃, 2016, 31(4): 396-402.

Qian Zhengyao, Li Guangping, Li Jiao, Liang Xue, Xu Zhao, Chen Yan, Zhao Hui. Relationship between PCSK9 and inflammation factor expression in ox-LDL-induced endothelial cells apoptosis[J]. Clinical Focus, 2016, 31(4): 396-402.

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https://huicui.hebmu.edu.cn/CN/Y2016/V31/I4/396

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氧化型低密度脂蛋白诱导内皮细胞凋亡中前蛋白转化酶枯草溶菌素9与炎症因子的关系

Relationship between PCSK9 and inflammation factor expression in ox-LDL-induced endothelial cells apoptosis

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[1]	吕丽丽, 翟满满, 丁小艳, 陈永清. 线粒体转录因子A介导的线粒体功能障碍在糖尿病心肌病中的作用[J]. 临床荟萃, 2023, 38(5): 465-468.
[2]	仇菊梅, 张琦, 刘静, 余静, 张雅娟. ox-LDL/LOX-1信号通路在糖尿病相关疾病中的研究进展[J]. 临床荟萃, 2023, 38(1): 79-83.
[3]	尹惠阳, 蔺雪峰, 韩轩茂. 蛋白激酶B通路、乙酰肝素酶、NADPH氧化酶在心肌缺血再灌注损伤中的作用及相互关系的研究进展[J]. 临床荟萃, 2022, 37(5): 459-462.
[4]	叶蒙蒙, 李旎, 徐国栋, 邵国丰. miR-361在心血管疾病的研究进展[J]. 临床荟萃, 2021, 36(9): 843-849.
[5]	刘明明, 李欣宇. LDL-C/HDL-C在2型糖尿病合并冠心病中的预测价值[J]. 临床荟萃, 2020, 35(4): 340-343.
[6]	张令霞，聂倩，郝志华，刘承浩，王忠丽，陈菲菲，刘焕欣. 室内外工作环境对心血管系统炎性标志物的影响[J]. 临床荟萃, 2020, 35(3): 224-227.
[7]	姜雯雯1，宋雅伟2，祁媚姣1，李小娟3，刘玉梅1. NGAL、炎症细胞因子在2型糖尿病肾脏疾病患者体内的变化[J]. 临床荟萃, 2020, 35(3): 238-241.
[8]	李灏，蔡勇，黄金波，袁莉，杨职. 缺血性脑卒中患者载脂蛋白及血浆脂蛋白相关磷脂酶A2与TOAST病因分型的研究[J]. 临床荟萃, 2018, 33(4): 298-301.
[9]	李晓群1，雒芳2，罗怡2，陶俊全3. 不同血糖水平2型糖尿病患者血脂特点分析[J]. 临床荟萃, 2017, 32(4): 314-316,322.
[10]	贺淑琴a，张雪银b. 肿瘤坏死因子α、超敏C反应蛋白、低密度脂蛋白胆固醇与老年急性脑梗死的相关性[J]. 临床荟萃, 2016, 31(9): 983-985,989.
[11]	郭文选,朱瀛谦,沈方臻,王晓妮,潘飞,陈晶. Wnt信号通路抑制剂XAV939对人小细胞肺癌H446增殖及凋亡的影响[J]. 临床荟萃, 2016, 31(5): 543-546.
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[13]	钱正瑶, 李广平. PSCK9在动脉粥样硬化中的作用[J]. 临床荟萃, 2016, 31(1): 108-111.
[14]	耿学丽;武英伟;陈向华;宗春光;肖丽君;宋鸿儒. 类风湿性关节炎患者血脂水平分析[J]. 临床荟萃, 2015, 30(7): 792-795.
[15]	李娇;李广平. 前蛋白转化酶枯草溶菌素9在动脉粥样硬化中的作用[J]. 临床荟萃, 2015, 30(3): 341-344.