淋巴管分泌信号Hspg2通过PI3K/AKT通路改善缺氧/复氧诱导的内皮功能障碍
Lymphoangiocrine signal Hspg2 improves hypoxia/reoxygenation-induced endothelial dysfunction through PI3K/AKT pathway
孙菡阳 1廖小婷 1张艳 1曾彬1
作者信息
- 1. 武汉大学人民医院心内科/心血管病湖北省重点实验室/武汉大学心血管病研究所 湖北 武汉 430060
- 折叠
摘要
目的:探讨淋巴管分泌信号硫酸肝素蛋白多糖2(Hspg2)对缺氧/复氧(H/R)诱导的人脐静脉内皮细胞(HUVECs)功能障碍的影响及作用机制.方法:将HUVECs细胞分为control组、H/R组、H/R+Hspg2组、H/R+Hspg2+LY294002(PI3K抑制剂)组.采用qRT-PCR检测细胞H/R后Hspg2 mRNA水平;一氧化氮(NO)试剂盒检测NO产量;通过Western Blot检测内皮损伤相关蛋白(eNOS、ICAM-1、VCAM-1)、炎症小体(NLRP3、Caspase-1)及PI3K/AKT通路相关蛋白表达.结果:Hspg2在H/R细胞中mRNA水平显著高于正常细胞.与H/R组相比,Hspg2处理显著增加了NO产生及eNOS蛋白表达,ICAM-1、VCAM-1及NLRP3、Caspase-1蛋白水平显著降低,p-PI3K/PI3K及p-AKT/AKT的水平显著升高.抑制PI3K/AKT通路显著减弱了Hspg2对H/R诱导的内皮功能障碍的保护作用.结论:Hspg2通过激活PI3K/AKT信号通路改善H/R诱导的HUVECs功能障碍.
Abstract
Objective:To investigate the effect and mechanism of lymphoangiocrine signal heparan sulfate proteoglycan 2(Hspg2)on hypoxia/reoxygenation(H/R)-induced dysfunction of human umbilical vein endothelial cells(HUVECs).Methods:HUVECs were divided into the control group,H/R group,H/R+Hspg2 group,and H/R+Hspg2+LY294002(PI3K inhibitor)group.qRT-PCR was used to detect the level of Hspg2 mRNA in H/R cells;Nitric oxide(NO)assay kit was used to detect NO pro-duction;Western Blot was used to detect the expression of endothelial injury-related proteins(eNOS,ICAM-1,and VCAM-1),inflammasomes(NLRP3 and Caspase-1),and PI3K/AKT pathway related proteins.Results:The mRNA level of Hspg2 in H/R was significantly higher than that in normal cells.Compared with the H/R group,Hspg2 treatment significantly increased NO production and eNOS protein expression.The levels of ICAM-1,VCAM-1,NLRP3,and Caspase-1 proteins were significantly reduced,while the protein expression levels of p-PI3K/PI3K and p-AKT/AKT were sig-nificantly increased.Inhibition of the PI3K/AKT pathway significantly weakened the protective effect of Hspg2 on H/R-induced endothelial dysfunction.Conclusion:Hspg2 improves H/R-induced HU-VECs dysfunction by activating the PI3K/AKT signaling pathway.
关键词
Hspg2/内皮功能障碍/脐静脉内皮细胞/PI3K/AKT信号通路/炎症小体Key words
Hspg2/Endothelial Dysfunction/Umbilical Vein Endothelial Cells/PI3K/AKT Signaling Pathway/Inflammasome引用本文复制引用
出版年
2024
NETL
NSTL
万方数据