JAK/STAT信号通路在高糖诱导人脐静脉内皮细胞损伤中的作用  

Role of JAK/STAT signaling pathway in high glucose-induced damage in human umbilical vein endothelial cells

作　　者：廖静秋[1,2] 林佳琼 张伟杰[2] 许翎[2] 智喜梅[2] 林凯[2] 吴文[2] 

机构地区：[1]南方医科大学,广东广州510515 [2]广东省人民医院广东省医学科学院广东省老年医学研究所东病区内分泌科,广东广州510080

出　　处：《中国病理生理杂志》2016年第3期392-397,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81450062);广东省自然科学基金资助项目(No.2015A030313872)

摘　　要：目的：探讨Janus激酶/信号转导子及转录激活子（JAK/STAT）信号通路是否介导高糖诱导的人脐静脉内皮细胞（HUVECs）损伤。方法：CCK-8检测细胞存活率;Western blot法检测内皮细胞JAK2、STAT3、caspase-9和内皮型一氧化氮合酶（e NOS）的表达水平;DCFH-DA染色荧光显微镜照相法检测内皮细胞内活性氧簇（ROS）水平;罗丹明123染色荧光显微镜照相法测定线粒体膜电位（MMP）。结果：高糖（40 mmol/L葡萄糖）处理HUVECs 6-12 h能上调JAK2的磷酸化,于9 h达最高峰;高糖处理HUVECs 6-12 h能上调p-STAT3水平,其中12 h表达最多;JAK/STAT通路抑制剂AG490预处理1 h可显著抑制由高糖引起的内皮细胞损伤,表现为细胞存活率升高、凋亡相关蛋白caspase-9表达和胞内ROS生成减少、MMP及e NOS表达升高。结论：JAK/STAT信号通路参与了高糖诱导的人脐静脉内皮细胞损伤过程。AIM：To investigate whether Janus kinase/signal transducer and activator of transcription（ JAK/STAT） signaling pathway mediates high glucose-induced damage in human umbilical vein endothelial cells（ HUVECs）.METHODS：The cell viability was examined by CCK-8 assay.The expression levels of JAK2,STAT3,caspase-9 and endothelial nitric oxide synthase（ e NOS） were detected by Western blot.The intracellular levels of reactive oxygen species（ ROS） were tested by DCFH-DA staining followed by photofluorography.Mitochondrial membrane potential（ MMP） was measured by rhodamine 123 staining followed by photofluorography.RESULTS：Treatment of HUVECs with high glucose（ 40 mmol/L glucose） for 6 - 12 h enhanced the protein level of phosphorylated JAK2,peaking at 9 h.Treatment of the cells with high glucose for 6 - 12 h also increased the protein level of p-STAT3 with the peak value at 12 h.Pretreatment with the inhibitor of JAK/STAT pathway AG490 for 1 h before exposure of the HUVECs to high glucose significantly inhibited the high glucose-induced injury,as evidenced by an increase in the cell viability,decreases in the expression of caspase-9 and the intracellular ROS production,and increases in MMP and the expression of e NOS.CONCLUSION：JAK/STAT signaling pathway is involved in the high glucose-induced damage in HUVECs.

关 键 词：JAK/STAT信号通路 高糖 人脐静脉内皮细胞 AG490 

分 类 号：R363.2[医药卫生—病理学] R587.2[医药卫生—基础医学]