沙格列汀抑制NF-κB信号通路下调LPS诱导的人肾小管上皮HK-2细胞MCP-1的表达  

Saxagliptin down-regulates LPS-induced MCP-1 expression via inactivation of NF-κB in human proximal tubular epithelial cells

作　　者：何蓉[1] 李清福[1] 夏缨[2] 李晓艳[1] 何彦蓉[1] 张维[3,4] 李露[5] 

机构地区：[1]成都军区机关医院内分泌科,四川成都610000 [2]成都军区机关医院第二门诊部,四川成都610000 [3]成都军区机关医院 [4]成都医学院第一附属医院,四川成都610500 [5]四川大学华西医院,四川成都610041

出　　处：《西部医学》2015年第10期1460-1463,共4页Medical Journal of West China

基　　金：四川省教育厅科研课题(11ZB172)

摘　　要：目的探讨二肽基肽酶4(DPP-4)竞争性抑制剂沙格列汀(saxagliptin)对脂多糖(LPS)诱导状态下人肾小管上皮HK-2细胞MCP-1表达的调节作用及相关的分子机制。方法将人肾小管上皮细胞HK-2细胞分为3组,分别为对照组(Control组)、LPS+沙格列汀(LPS+SAX组)和LPS组。在干预12小时后使用RT-PCR法和western blot法对HK-2细胞MCP-1mRNA和蛋白的表达水平进行检测;并使用western blot法对HK-2细胞NF-κB p65活化水平(phospho-NF-κB p65/total NF-κB p65比值)进行分析。结果与Control组相比较,在LPS干预12小时后HK-2细胞MCP-1mRNA和蛋白的表达水平以及phospho-NF-κB p65/total NF-κB p65比值均明显升高,差异均有统计学意义(P<0.05);但LPS组较LPS+SAX组MCP-1mRNA和蛋白的表达的升高以及phospho-NF-κB p65/total NF-κB p65比值的增加更加显著,差异均有统计学意义(P<0.05)。结论 DPP-4抑制剂沙格列汀可以通过抑制NF-κB的磷酸化下调LPS诱导的人肾小管上皮HK-2细胞MCP-1合成和释放并对其产生保护作用。Objective To explore whether saxagliptin could down-regulate LPS-induced MCP-1expression in human proximal tubular epithelial cells,and its potential molecular mechanism.Methods Human proximal tubular epithelial cells（HK-2cells）were divided into 3groups,Control group,LPS＋saxagliptin group（LPS＋SAX group）and LPS group.RT-PCR was used to measure the mRNA expression of MCP-1.The protein expression of MCP-1and the phosphorylation level of NF-κB p65 were analyzed by western blot.Results After 12 hours LPS stimulation,the mRNA and protein expression of MCP-1were remarkably up-regulated,and the ratio of phospho-NF-κB p65/total NF-κB p65 were sharply raised.Then,LPS-induced the up-regulation of MCP-1and the raised ratio of phospho-NF-κB p65/total NF-κB p65 were all noticeably inhibited by saxagliptin in HK-2cells.Conclusion Saxagliptin down-regulates LPS-induced MCP-1expression possibly via inhibition of NF-κB in human proximal tubular epithelial cells（HK-2cells）.

关 键 词：沙格列汀 HK-2细胞 单核细胞趋化蛋白-1(MCP-1) 核转录因子-κB(NF-κB) 

分 类 号：R446[医药卫生—诊断学]