甘草苷上调丙酮酸激酶M2表达促进人脐静脉内皮细胞损伤后血管新生  

Liquiritin promotes angiogenesis of human umbilical vein endothelial cells after injury through up-regulating pyruvate kinase M2 expression

作　　者：孙菡阳 张艳[1] 廖小婷 曾彬[1] SUN Hanyang;ZHANG Yan;LIAO Xiaoting;ZENG Bin(Dept.of Cardiology,Renmin Hospital of Wuhan University/Cardiovascular Research Institute of Wuhan University/&Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China)

机构地区：[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

出　　处：《武汉大学学报（医学版）》2024年第10期1165-1169,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:81570333,81270271);国家自然科学基金青年基金资助项目(编号:30900609);中央高校基本科研业务费专项资金(编号:2042020kf1014)。

摘　　要：目的:探讨甘草苷(LIQ)上调丙酮酸激酶M2(PKM2)表达对过氧化氢(H_(2)O_(2))诱导人脐静脉内皮细胞(HUVECs)血管新生的影响及可能机制。方法:使用H_(2)O_(2)诱导HUVECs损伤,将细胞分为对照组、H_(2)O_(2)组、H_(2)O_(2)+LIQ组、H_(2)O_(2)+LIQ+Shikonin(PKM2抑制剂)组、H_(2)O_(2)+LIQ+Stattic(STAT3抑制剂)组。采用细胞划痕及管腔形成实验检测细胞迁移、成管能力,Western Blot检测血管新生关键蛋白VEGF、FGF2的表达,以及PKM2、磷酸化PKM2(p-PKM2)和PKM2下游激酶STAT3、p-STAT3的蛋白表达。结果:与H_(2)O_(2)组相比,LIQ处理显著提高了细胞迁移、成管能力,并增加VEGF、FGF2和PKM2、p-PKM2的表达水平;LIQ上调PKM2表达,显著增加了STAT3、p-STAT3表达水平。与H_(2)O_(2)+LIQ组相比,抑制PKM2或STAT3后细胞迁移、成管能力显著下降,VEGF、FGF2、STAT3及p-STAT3蛋白升高趋势被逆转。结论:LIQ可通过上调PKM2表达激活STAT3信号通路促进H_(2)O_(2)诱导的HUVECs血管新生。Objective:To investigate whether liquiritin(LIQ)up-regulation of pyruvate kinase M2(PKM2)on the angiogenesis of human umbilical vein endothelial cells(HUVECs)induced by hydrogen peroxide(H_(2)O_(2))and its possible mechanism.Methods:HUVECs were damaged by H_(2)O_(2),and the cells were divided into the control group,H_(2)O_(2) group,H_(2)O_(2)+LIQ group,H_(2)O_(2)+LIQ+Shikonin(PKM2 inhibitor)group,and H_(2)O_(2)+LIQ+Static(STAT3 inhibitor)group.Cell migration and tubular formation ability were detected by cell scratch and lumen formation assay.Western Blot was used to detect the expression of key angiogenic proteins VEGF and FGF2,and the expression of proteins,PKM2 and phosphorylationp-PKM2(p-PKM2),and PKM2 downstream kinase STAT3/p-STAT3.Results:Compared with the H_(2)O_(2) group,LIQ treatment significantly improved cell migration and tubeforming ability,and the expression levels of VEGF,FGF2,PKM2,and p-PKM2.LIQ up-regulated PKM2 expression and significantly increased the expression levels of STAT3 and p-STAT3.Compared with those in the H_(2)O_(2)+LIQ group,cell migration,and tube-forming ability were significantly decreased after PKM2 or STAT3 inhibition,and the increasing trend of VEGF,FGF2,STAT3,and p-STAT3 proteins was reversed.Conclusion:LIQ can activate the STAT3 signaling pathway by upregulating PKM2 expression to promote H_(2)O_(2)-induced angiogenesis in HUVECs.

关 键 词：丙酮酸激酶M2 甘草苷 脐静脉内皮细胞 血管新生 STAT3信号通路 

分 类 号：R54[医药卫生—心血管疾病]