可溶性环氧化物水解酶抑制剂对小鼠内皮祖细胞分泌血管内皮生长因子及缺氧诱导因子-1α的促进作用  

Effects of soluble epoxide hydrolase inhibitors on secretion of vascular endothelial growth factor and hypoxia-inducible factor-1αby murine endothelial progenitor cells

作　　者：王振河[1] 姜德谦[2] 许丹焰[2] 李卫华[1] 谢强[1] WANG Zhenhe;JIANG Deqian;XU Danyan;LI Weihua;XIE Qiang(Department of Cardiology,the First Affiliated Hospital of Xiamen University,Xiamen,Fujian 361003,China)

机构地区：[1]厦门大学附属第一医院心内科,厦门361003 [2]中南大学湘雅二医院心内科

出　　处：《福建医药杂志》2021年第4期128-132,F0003,共6页Fujian Medical Journal

基　　金：福建省卫生厅青年科研课题(2013-2-84)。

摘　　要：目的探讨可溶性环氧化物水解酶抑制剂(t-AUCB)能否促进小鼠来源内皮祖细胞(EPCs)分泌内皮生长因子(VEGF)和缺氧诱导因子-1α(HIF-1α),及可能的相关机制。方法提取小鼠长骨骨髓,离心分离培养,取得高纯度EPCs,不同浓度可溶性环氧化物水解酶抑制剂(t-AUCB)和过氧化体增殖物激活型受体γ(PPAR-γ)阻断剂GW9662单独或联合干预EPCs,Western blot检测上述EPCs体外分泌VEGF及HIF-1α情况。结果从0~100μmol/L,t-AUCB呈浓度依赖性增强EPCs体外分泌VEGF、HIF-1α能力,而5μmol/L t-AUCB阻断剂GW9662可抑制EPC上述功能。1、10、50、100μmol/L t-AUCB促进EPCs分泌VEGF、HIF-1α能力与0μmol/L t-AUCB相比,差异均具有统计学意义(P<0.05);GW9662+100μmol/L t-AUCB与100μmol/L t-AUCB比较,差异具有统计学意义(P<0.05),与0μmol/L tAUCB比较,差异也具有统计学意义(P<0.05)。结论t-AUCB可促进EPCs分泌VEGF及HIF-1α,其机制可能与激活PPAR-γ通路有关。Objective To investigate whether soluble epoxide hydrolase inhibitors(t-AUCB)can promote the secretion of vascular endothelial growth factor(VEGF)and hypoxia-inducible factor-1α(HIF-1α)in murine endothelial progenitor cells(EPCs),and the possible related mechanisms.Methods Long bone marrow of mice was extracted and centrifugally cultured to obtain high purity EPCs.Different concentrations of soluble epoxide hydrolase inhibitor(t-AUB)and peroxide proliferator-activated receptorγ(PPAR-γ)blocker GW9662 were used to interfere with EPCs alone or in combination.The secretion of VEGF and HIF-1αin vitro of EPCs was detected by Western blot.Results From 0 to 100μmol/L,t-AUCB enhanced the ability of EPCs to secrete VEGF and HIF-1αin a concentration dependent manner,while 5μmol/L t-AUCB blocker GW9662 inhibited the above functions of EPCs.Compared with 0μmol/L t-AUCB,1,10,50 and 100μmol/L t-AUCB promoted the secretion of VEGF and HIF-1αin EPCs,and the differences were statistically significant(P<0.05).The difference between GW9662+100μmol/L t-AUCB and 100μmol/L t-AUCB was statistically significant(P<0.05),compared with 0μmol/L t-AUCB,the difference was also statistically significant(P<0.05).Conclusion t-AUCB can promote the secretion of VEGF and HIF-1αin EPCs,and the mechanism may be related to the activation of PPAR-γpathway.

关 键 词：可溶性环氧化物水解酶抑制剂 t-AUCB 过氧化体增殖物激活型受体Γ 血管内皮生长因子 缺氧诱导因子-1Α 内皮祖细胞 

分 类 号：R363[医药卫生—病理学]