摘要
目的:探讨阿托伐他汀干预对内皮细胞微粒(EMPs)诱导的人脐静脉内皮细胞(HUVEC)ERK/MAPK和NF-κB信号通路及细胞间黏附分子-1(ICAM-1)表达的影响。方法:将体外培养的HUVEC细胞系ECV-304分组培养:①EMPs不同作用时间组用EMPs(终浓度105mL-1)分别刺激细胞0、3、6、12和24h。②EMPs不同作用剂量组分别用终浓度为0、102、103、104及105mL-1的EMPs刺激细胞24h。③抑制剂预处理组在EMPs刺激前,分别用ERK、p38MAPK及NF-κB抑制剂PD98059、SB203580、PDTC进行预处理。④阿托伐他汀预处理组在EMPs刺激前,用阿托伐他汀进行预处理。然后,用实时荧光定量PCR测定细胞中ICAM-1mRNA的表达,Westernblot法测定磷酸化ERK(p-ERK)、p-p38MAPK、NF-κBp65蛋白的表达。结果:随EMPs作用时间的延长和作用剂量的增加,细胞p-ERK、p-p38MAPK、NF-κBp65蛋白及ICAM-1mRNA的表达均逐渐增加(P均<0.001)。用上述抑制剂及阿托伐他汀预处理后,EMPs诱导的细胞ICAM-1mRNA表达均降低(P<0.05)。结论:阿托伐他汀可能通过ERK/MAPK和NF-κB信号通路下调EMPs诱导的内皮细胞ICAM-1的表达。
Aim：To observe the effects of atorvastatin on ERK,p38MAPK and nuclear factor-κB（NF-κB） and intercellular adhesion molecule 1（ICAM-1） expressions in endothelial microparticles（EMPs）-induced human umbilical vein endothelial cells（HUVECs）.Methods：The cultured HUVECs were cultured with EMPs of 105 mL-1for 0,3,6,12,and 24 h.The HUVECs were cultured with 0,102,103,104,105 mL-1 EMPs for 24 h.The HUVECs were pretreated with ERK inhibitor（PD98059）,p38 inhibitor（SB203580）,NF-κB inhibitor（PDTC）,or atorvastatin,then were treated with EMPs.The ICAM-1 mRNA level was detected by Real-time-PCR.Western blot was performed to determine the expression levels of phospho-ERK（p-ERK）,p-p38MAPK and NF-κB p65 proteins.Results：With the increase of dose and exposure time of EMPs,the expression levels of ICAM-1 mRNA,p-ERK,p-p38MAPK and NF-κB p65 protein in HUVECs obviously increased（P0.001）.After the pretreatment of the inhibitors mentioned above and atorvastatin,the ICAM-1 mRNA expression decreased（P0.05）.Conclusion：Atorvastatin could downregulate ICAM-1 expression in EMPs-induced HUVECs by blocking ERK/MAPK and NF-κB signaling pathway.
出处
《郑州大学学报（医学版）》
CAS
北大核心
2012年第6期765-769,共5页
Journal of Zhengzhou University(Medical Sciences)
基金
广西自然科学基金青年基金资助项目2012GXNSFBA053113
广西卫生厅自筹经费科研项目Z2011103
关键词
内皮细胞微粒
脐静脉内皮细胞
丝裂素活化蛋白激酶
细胞间黏附分子-1
阿托伐他汀
endothelial microparticle
human umbilical vein endothelial cell
mitogen-activated protein kinase
intercellular adhesion molecule 1
atorvastatin
