武汉市第一医院(武汉市中西医结合医院)儿科;
目的 基于缺氧诱导因子-1α(HIF-1α)/Bcl2/腺病毒E1B相互作用蛋白3(BNIP3)通路的糖酵解探讨氧诱导新生小鼠视网膜血管生成机制。方法 将人脐静脉内皮细胞(HUVECs)分为常氧组、缺氧+si-NC组、缺氧+si-HIF-1α组和缺氧+si-HIF-1α+BNIP3组。常氧组HUVECs暴露于常氧(21%O_2)下培养。缺氧+si-NC组、缺氧+si-HIF-1α组和缺氧+si-HIF-1α+BNIP3组用si-NC、si-HIF-1α或si-HIF-1α联合BNIP3质粒处理HUVECs 36 h,然后暴露于缺氧(1%O_2)下培养。通过免疫荧光、代谢测量、细胞活力、划痕实验、管形成实验考察细胞线粒体自噬、糖酵解以及增殖、迁移和管形成情况。出生后第7天的C57BL/6J幼鼠随机分配到不同的治疗组：对照组、氧诱导视网膜病变(OIR)组、OIR+si-HIF-1α组和OIR+si-BNIP3组，测量新生血管形成和血管闭塞情况。结果 与常氧组比较，缺氧+si-NC组HUVECs中LC3+MitoTracker+斑点数、葡萄糖摄取和乳酸释放的速率增加(P<0.001)。与缺氧+si-NC组比较，缺氧+si-HIF-1α组HUVECs中LC3+MitoTracker+斑点数、葡萄糖摄取和乳酸释放的速率降低(P<0.01)。与常氧组比较，缺氧+si-NC组HUVECs在培养第72 h的增殖活性降低(P<0.05),并且伤口愈合面积和管形成数量增加(P<0.01)。与缺氧+si-NC组比较，缺氧+si-HIF-1α组HUVECs在培养第24、48、72小时的增殖活性降低(P<0.05),伤口愈合面积、管形成数量降低(P<0.001)。BNIP3的过表达逆转了HIF-1α敲低对线粒体自噬、糖酵解以及生物学功能的影响。与OIR组比较，OIR+si-HIF-1α组和OIR+si-BNIP3组小鼠的视网膜组织中新生血管形成和血管闭塞区域减少(P<0.05)。结论 HIF-1α/BNIP3信号通路在低氧条件下促进了HUVECs中线粒体自噬激活，其对于内皮功能和血管生成的调控有重要作用。
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.02.006
中图分类号:R774.1
引用信息:
[1]易燕,陈斐斐,谭赟等.HIF-1α/BNIP3通路介导的糖酵解与氧诱导新生小鼠视网膜血管生成的关系[J].安徽医科大学学报,2025,60(02):226-233.DOI:10.19405/j.cnki.issn1000-1492.2025.02.006.
基金信息:
湖北省自然科学基金(编号：2019CFB401)~~