中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (13): 3280-3287.doi: 10.12307/2025.579

• 脐带脐血干细胞 umbilical cord blood stem cells • 上一篇    下一篇

脂多糖调控人脐静脉内皮细胞的功能

佘  旭1，李晓江1，2，黄海霞3，万玲玲1，罗青清1，4   

  1. 1西南医科大学附属医院产科，四川省泸州市   646000；2古蔺县人民医院妇产科，四川省泸州市   646599；3南昌大学第一附属医院产科，江西省南昌市   330038；4北京大学国际医院妇产科，北京市   102206
  • 收稿日期:2025-01-24 修回日期:2025-03-22 接受日期:2025-04-22 出版日期:2026-05-08 发布日期:2025-12-25
  • 通讯作者: 罗青清，博士，副主任医师，西南医科大学附属医院产科，四川省泸州市 646000；北京大学国际医院妇产科，北京市 102206
  • 作者简介:佘旭，女，1999年生，四川省达州市人，汉族，西南医科大学在读硕士，主要从事妊娠期高血压、妊娠期糖尿病等方面的研究。
  • 基金资助:
    四川省自然科学基金项目(2022NSFSC1373)，项目负责人：罗青清；古蔺县人民医院-西南医科大学附属医院科技战略合作项目(2022GLX-NYDFY07)，项目负责人：罗青清；泸州市社会发展重点科技专项(2021-SYF-27)，项目负责人：罗青清

Lipopolysaccharides regulate the function of human umbilical vein endothelial cells

She Xu1, Li Xiaojiang1, 2, Huang Haixia3, Wan Lingling1, Luo Qingqing1, 4   

  1. 1Department of Obstetrics, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Department of Obstetrics and Gynecology, Gulin County People’s Hospital, Luzhou 646599, Sichuan Province, China; 3Department of Obstetrics, First Affiliated Hospital of Nanchang University, Nanchang 330038, Jiangxi Province, China; 4Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing 102206, China
  • Received:2025-01-24 Revised:2025-03-22 Accepted:2025-04-22 Online:2026-05-08 Published:2025-12-25
  • Contact: Luo Qingqing, MD, Associate chief physician, Department of Obstetrics, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing 102206, China
  • About author:She Xu, Master candidate, Department of Obstetrics, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    Sichuan Natural Science Foundation Project, No. 2022NSFSC1373 (to LQQ); Gulin County People's Hospital-Southwest Medical University Affiliated Hospital Science and Technology Strategic Cooperation Project, No. 2022GLX-NYDFY07 (to LQQ); Key Science and Technology Project for Social Development in Luzhou City, No. 2021-SYF-27 (to LQQ)

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摘要：

文题释义：

核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体：是一种多聚体蛋白复合物，由模式识别受体蛋白NLRP3、含CARD的凋亡相关斑点样蛋白(ASC)和效应蛋白前Caspase-1组成。当机体受到细菌、病毒等刺激时，NLRP3被激活并与ASC结合，ASC募集并活化Caspase-1，活化的Caspase-1将无活性的促炎因子白细胞介素1β和白细胞介素18前体蛋白剪切加工为成熟的细胞因子白细胞介素1β和白细胞介素18，进一步增加局部炎性基因表达，从而参与诱导炎症反应及组织损伤。
6-磷酸果糖-2-激酶3(PFKFB3)：是糖酵解的关键酶，每1分子葡萄糖经过糖酵解可产生2分子ATP和2分子丙酮酸，且该过程不消耗氧气，内皮细胞中85%以上的ATP是通过糖酵解产生的，糖酵解异常可导致内皮细胞功能障碍。

摘要
背景：血管内皮细胞功能障碍为子痫前期发病的核心因素，脂多糖可用于建立子痫前期大鼠模型，但对内皮细胞的影响及机制尚未完全明确。
目的：探讨脂多糖对人脐静脉内皮细胞功能的影响及可能存在的机制。
方法：将人脐静脉内皮细胞分为对照组和脂多糖组，通过下列实验检测脂多糖处理后两组人脐静脉内皮细胞功能变化：细胞黏附实验检测人脐静脉内皮细胞对单核细胞的黏附性；小管形成实验检测人脐静脉内皮细胞的小管形成能力；qPCR检测核苷酸结合寡聚化结构域样受体蛋白3、白细胞介素1β、6-磷酸果糖-2-激酶及内皮型一氧化氮合酶 mRNA表达水平；Western blot检测核苷酸结合寡聚化结构域样受体蛋白3、6-磷酸果糖-2-激酶3、细胞间黏附分子1及内皮型一氧化氮合酶蛋白表达水平。人脐静脉内皮细胞分为对照组、脂多糖组和MCC950(核苷酸结合寡聚化结构域样受体蛋白3抑制剂)组，qPCR检测核苷酸结合寡聚化结构域样受体蛋白3、白细胞介素1β、6-磷酸果糖-2-激酶3及内皮型一氧化氮合酶 mRNA表达水平。
结果与结论：①与对照组相比，脂多糖组细胞间黏附分子1蛋白表达量增加(P < 0.05)，单核细胞黏附数量增多(P < 0.05)，提示人脐静脉内皮细胞活化，黏附能力增强；②与对照组相比，脂多糖能抑制人脐静脉内皮细胞的小管形成能力(P < 0.05)；③与对照组相比，脂多糖组内皮型一氧化氮合酶的mRNA及蛋白表达量减少(P < 0.05)，核苷酸结合寡聚化结构域样受体蛋白3、白细胞介素1β、6-磷酸果糖-2-激酶mRNA表达量以及核苷酸结合寡聚化结构域样受体蛋白3、6-磷酸果糖-2-激酶3蛋白表达量增加(P < 0.05)；④与脂多糖组相比，MCC950组白细胞介素1β和6-磷酸果糖-2-激酶3 mRNA表达量减少以及内皮型一氧化氮合酶 mRNA表达量增加(P < 0.05)。结果表明，脂多糖可通过核苷酸结合寡聚化结构域样受体蛋白3/白细胞介素1β/6-磷酸果糖-2-激酶3途径诱导人脐静脉内皮细胞功能障碍。

关键词: 脂多糖, 内皮细胞, 核苷酸结合寡聚化结构域样受体蛋白3(NLRP3), 白细胞介素1β, 6-磷酸果糖-2-激酶3(PFKFB3), 子痫前期

Abstract: BACKGROUND: Vascular endothelial cell dysfunction is the core factor in the pathogenesis of preeclampsia. Lipopolysaccharide can be used to establish a rat model of preeclampsia, but the effect and mechanism on endothelial cells have not been fully clarified.
OBJECTIVE: To investigate the effect of lipopolysaccharides on the function of human umbilical vein endothelial cells and its possible mechanism.
METHODS: Human umbilical vein endothelial cells were divided into control group and lipopolysaccharides group. The functional changes of human umbilical vein endothelial cells after lipopolysaccharides treatment in both groups were detected by the following experiments: Cell adhesion test was used to detect the adhesion of monocytes to human umbilical vein endothelial cells. Tubule formation experiment was used to detect the tubule formation ability of human umbilical vein endothelial cells. The mRNA expression levels of nucleotide binding oligomerization domain-like receptor protein 3, interleukin-1β, 6-phosphofructo-2-kinase and endothelial nitric oxide synthase were detected by qPCR. Western blot assay was utilized to detect the protein expression levels of nucleotide binding oligomerization domain-like receptor protein 3, 6-phosphofructo-2-kinase 3, intercellular adhesion molecule 1, and endothelial nitric oxide synthase. Human umbilical vein endothelial cells were divided into control group, lipopolysaccharide group, and MCC950 (nucleotide binding oligomerization domain-like receptor protein 3 inhibitor) group. qPCR was used to detect the mRNA expression levels of nucleotide binding oligomerization domain-like receptor protein 3, interleukin-1β, 6-phosphofructo-2-kinase 3 and endothelial nitric oxide synthase.
RESULTS AND CONCLUSION: (1) Compared with the control group, the expression of intercellular adhesion molecule-1 protein in lipopolysaccharides group increased (P < 0.05), and the adhesion of monocytes increased (P < 0.05), suggesting that human umbilical vein endothelial cells were activated and their adhesion ability was enhanced. (2) Compared with the control group, the tubule formation ability of human umbilical vein endothelial cells was inhibited in the lipopolysaccharides group (P < 0.05). (3) Compared with the control group, the mRNA and protein expression levels of endothelial nitric oxide synthase were decreased in the lipopolysaccharides group (P < 0.05); mRNA expression levels of nucleotide binding oligomerization domain-like receptor protein 3, interleukin-1β, and 6-phosphofructo-2-kinase, as well as the protein expression levels of nucleotide binding oligomerization domain-like receptor protein 3 and 6-phosphofructo-2-kinase 3 were increased (P < 0.05). (4) Compared with the lipopolysaccharides group, the mRNA expressions of interleukin-1β and 6-phosphofructo-2-kinase 3 were decreased, and the mRNA expression of endothelial nitric oxide synthase was increased in the MCC950 group (P < 0.05). The results suggest that lipopolysaccharides can cause dysfunction of human umbilical vein endothelial cells, which may be regulated by the nucleotide-binding oligomerization domain-like receptor protein 3/interleukin-1β/6-phosphofructo-2-kinase 3 pathway. 

Key words: lipopolysaccharides, endothelial cell, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), interleukin-1β, 6-phosphofructo-2-kinase 3 (PFKFB3), preeclampsia

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