虎杖苷通过调节JAK2/STAT3信号通路改善血管内皮细胞损伤的研究  

Polydatin protects vascular endothelial cells by modifying the JAK2/STAT3 signaling pathway

作　　者：孔稳稳 韦惠珍 徐媛颖 沙雯君 鲁郡 雷涛 Kong Wenwen;Wei Huizhen;Xu Yuanying;Sha Wenjun;Lu Jun;Lei Tao(Shanghai Putuo Central School of Clinical Medicine,Anhui Medical University,Shanghai 200062;The Fifth School of Clinical Medicine,Anhui Medical University,Hefei 230032;Dept of Endocrinology,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062)

机构地区：[1]安徽医科大学上海普陀中心临床学院,上海200062 [2]安徽医科大学第五临床医学院,合肥230032 [3]上海中医药大学附属普陀医院内分泌科,上海200062

出　　处：《安徽医科大学学报》2024年第7期1201-1205,1212,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金面上项目(编号:81774083);上海市普陀区卫生健康系统临床特色专科建设项目(编号:2020tszk01);上海市医学重点专科建设项目(编号:ZK2019B16);上海市普陀区卫生健康系统科技创新项目(编号:ptkwws202003);上海市卫生健康委员会课题(编号:202240309)。

摘　　要：目的探讨虎杖苷通过蛋白酪氨酸激酶2(JAK2)/信号传导与转录激活因子3(STAT3)信号通路对脂多糖(LPS)诱导的人脐静脉血管内皮细胞(HUVECs)损伤的保护作用。方法体外培养HUVECs,500 ng/ml LPS诱导其损伤,设为模型组;在模型组基础上,用不同浓度(10、20、40μmol/L)虎杖苷干预HUVECs 24 h,分别设置为虎杖苷低浓度组、虎杖苷中浓度组和虎杖苷高浓度组;另设对照组。CCK-8、单核细胞-内皮细胞黏附、划痕和Transwell实验检测细胞活力、黏附、迁移和侵袭能力;ELISA法检测细胞上清液中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量;Western blot法检测JAK2/STAT3信号通路相关蛋白表达水平。结果与对照组比较,模型组细胞存活率下降(P<0.01),细胞黏附、迁移及侵袭能力增强(P<0.001,P<0.05,P<0.01),细胞上清液中IL-6和TNF-α含量增加(P<0.001),细胞中JAK2和STAT3蛋白磷酸化水平升高(P<0.05)。与模型组比较,虎杖苷干预后,LPS损伤细胞情况减轻,虎杖苷低、中、高浓度组细胞存活率增加(P<0.05),细胞黏附、迁移和侵袭能力下降(P<0.05,P<0.05,P<0.001),细胞上清液中IL-6和TNF-α含量下降(P<0.05),细胞中JAK2和STAT3蛋白磷酸化水平降低(P<0.05)。结论虎杖苷能有效减轻LPS对HUVECs的炎性损伤,减少炎症因子分泌,抑制内皮细胞黏附、迁移和侵袭,其机制可能与虎杖苷下调JAK2/STAT3信号通路相关。Objective To study the protective effect of polydatin on lipopolysaccharide-induced injury of human umbilical vein vascular endothelial cells(HUVECs)through the protein Janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)signaling pathway.Methods HUVECs were cultured in vitro,and 500 ng/ml LPS induced their injury and set as a model group;based on the model group,endothelial cells were intervened with different concentrations concentration group,polydatin medium concentration group,and polydatin high concentration group,respectively;a control group was set as another group.CCK-8,monocyte-endothelial cell adhesion,scratch and Transwell assays were used to detect cell viability,adhesion,migration and invasive ability;ELISA was used to detect interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)levels in the cell supernatant;Western blot was used to detect the expression of proteins related to the JAK2/STAT3 signaling pathway levels of JAK2/STAT3 signaling pathway related proteins.Results Compared with the control group,the model group showed decreased cell survival(P<0.01),increased cell adhesion,migration and invasion(P<0.001,P<0.05,P<0.01),increased levels of IL-6 and TNF-αin the cell supernatant(P<0.001),and increased levels of phosphorylation of JAK2 and STAT3 proteins in the cells(P<0.05).Compared with the model group,LPS damage to cells was attenuated after polydatin intervention,cell survival was increased in polydatin low-,medium-and high-concentration groups(P<0.05),cell adhesion,migration,and invasion decreased(P<0.05,P<0.05,P<0.001),IL-6 and TNF-αlevels in cell supernatants decreased(P<0.05),and the levels of cellular JAK2 and STAT3 protein phosphorylation levels decreased(P<0.05).Conclusion Polydatin seems to reduce the inflammatory injury of human umbilical vein endothelial cells induced by LPS,reducing the secretion of inflammatory factors,and inhibiting the ability of cell adhesion,migration and invasion,which may be related to the down-regulation of JAK2/STAT3 sign

关 键 词：动脉粥样硬化 人脐静脉内皮细胞 虎杖苷 JAK2/STAT3信号通路 

分 类 号：R543.5[医药卫生—心血管疾病]