PCSK9降解ApoER2对ApoE/ApoER2抗炎作用的影响  

Effect of ApoER2 degradation by PCSK9 on the anti-inflammatory effect of ApoE/ApoER2

作　　者：赵伊梦 白雪琴 何俊锋 王萍 刘录山[1] ZHAO Yimeng;BAI Xueqin;HE Junfeng;WANG Ping;LIU Lushan(Institute of Cardiovascular Disease,University of South China&Key Laboratory for Arteriosclerology of Hunan Province&Human International Scientific and Technological Cooperation Base of Arteriosclerotic Disease,Hengyang,Hunan 421001,China;Changde Wuling District Center for Disease Control and Prevention,Changde,Hunan 415000,China)

机构地区：[1]南华大学心血管疾病研究所动脉硬化学湖南省重点实验室湖南省动脉硬化性疾病国际科技创新合作基地,湖南省衡阳市421001 [2]常德市武陵区疾病预防控制中心,湖南省常德市415000

出　　处：《中国动脉硬化杂志》2023年第5期375-382,共8页Chinese Journal of Arteriosclerosis

基　　金：湖南省自然科学基金项目(2021JJ30596);湖南省研究生科研创新项目(QL20220217)。

摘　　要：[目的]探讨前蛋白转化酶枯草溶菌素9(PCSK9)对载脂蛋白E(ApoE)受体2(ApoER2)的降解作用与ApoE/ApoER2抗炎作用之间的关系。[方法]体外培养人脐静脉内皮细胞(HUVEC)和HepG2细胞,采用Western blot和ELISA检测脂多糖(LPS)对HUVEC中Toll样受体(TLR4)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和PCSK9表达及分泌的影响;ApoE3对LPS诱导的HUVEC中TNF-α、IL-6、PCSK9和ApoER2表达及分泌的影响;ApoE的三种亚型(ApoE2、ApoE3和ApoE4)对非炎症状态下HUVEC和HepG2细胞中PCSK9及ApoER2表达的影响;PCSK9对HUVEC中ApoER2、TNF-α和IL-6表达及分泌的影响。[结果]Western blot和ELISA检测结果显示,LPS可以上调HUVEC中TLR4、TNF-α、IL-6和PCSK9的表达及分泌。ApoE3抑制LPS诱导的炎症反应,并上调ApoER2的表达及分泌。ApoE的三种亚型(ApoE2、ApoE3和ApoE4)对非炎症状态下HUVEC和HepG2细胞中PCSK9及ApoER2的表达无明显影响。不同剂量(0、0.5、1.0和2.5 mg/L)的人重组PCSK9处理HUVEC 24 h,Western blot和ELISA检测结果显示,PCSK9上调TNF-α、IL-6的表达及分泌,下调ApoER2的表达。[结论]PCSK9通过对ApoER2的降解来拮抗ApoE/ApoER2的抗炎作用。Aim To investigate the relationship between apolipoprotein E(ApoE)receptor 2(ApoER2)degradation by proprotein convertase subtilisin kexin 9(PCSK9)and the anti-inflammatory effect of ApoE/ApoER2.Methods Human umbilical vein endothelial cells(HUVEC)and HepG2 cells were cultured in vitro,Western blot and ELISA were used to detect the effects of lipopolysaccharide(LPS)on the expression and secretion of Toll-like receptor(TLR4),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and PCSK9 in HUVEC;the effects of ApoE3 on the expression and secretion of TNF-α,IL-6,PCSK9 and ApoER2 in HUVEC induced by LPS;the effects of three isoforms of ApoE(ApoE2,ApoE3 and ApoE4)on the expression of PCSK9 and ApoER2 in HUVEC and HepG2 cells under non-inflammatory conditions;and the effects of PCSK9 on the expression and secretion of ApoER2,TNF-αand IL-6 in HUVEC.Results Western blot and ELISA showed that LPS up-regulated the expression and secretion of TLR4,TNF-α,IL-6 and PCSK9 in HUVEC;ApoE3 inhibited LPS-induced inflammatory responses,and up-regulated ApoER2 expression and secretion;the three isoforms of ApoE(ApoE2,ApoE3 and ApoE4)had no effect on the expression of PCSK9 and ApoER2 in HUVEC and HepG2 cells under non-inflammatory conditions.Different doses(0,0.5,1.0 and 2.5 mg/L)of recombinant human PCSK9 were used to treat HUVEC for 24 h,Western blot and ELISA showed that PCSK9 up-regulated the expression and secretion of TNF-αand IL-6,and down-regulated the expression of ApoER2.Conclusion PCSK9 antagonizes the anti-inflammatory effects of ApoE/ApoER2 by degrading ApoER2.

关 键 词：炎症反应 前蛋白转化酶枯草溶菌素9 载脂蛋白E 载脂蛋白E受体2 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]