CITED2改善低氧/复氧诱导的人脐静脉内皮细胞线粒体功能

doi:10.16352/j.issn.1001-6325.2026.08.1109

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (8): 1109-1116.doi: 10.16352/j.issn.1001-6325.2026.08.1109

CITED2改善低氧/复氧诱导的人脐静脉内皮细胞线粒体功能

孙理华¹, 时司晏¹, 王维浩¹, 杨丽¹, 张培东^2*

1.中山市博爱医院心血管内科,广东中山 528400;
2.南方医科大学珠江医院(第二临床医学院),广东广州 510260

收稿日期:2025-06-11 修回日期:2025-09-24 发布日期:2026-07-22
通讯作者: ^*zhangpeidong1103@126.com
基金资助:
中山市社会公益科技研究项目(2023B1059)

CITED2 improves mitochondrial function in hypoxia/reoxygenation-induced human umbilical vein endothelial cells

SUN Lihua¹, SHI Siyan¹, WANG Weihao¹, YANG Li¹, ZHANG Peidong^2*

1. Department of Cardiology, Bo′ai Hospital of Zhongshan, Zhongshan 528400;
2. Zhujiang Hospital of Southern Medical University (the Second Clinical Medical College), Guangzhou 510260, China

Received:2025-06-11 Revised:2025-09-24 Published:2026-07-22
Contact: ^*zhangpeidong1103@126.com

摘要/Abstract

摘要： 目的探究富含谷氨酸/天冬氨酸羧基末端结构域的CBP/p300相互作用反式激活因子2(CITED2)在冠状动脉慢血流(CSF)患者中的表达及其对内皮细胞低氧/复氧(H/R)损伤的调控机制。方法收集CSF患者及健康对照人群外周血样本,用ELISA检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和活性氧(ROS)水平,RT-qPCR和Western blot分析外周血单个核细胞(PBMCs)中CITED2、HIF-1α、DRP1、SIRT1和MFN2的表达。体外培养人脐静脉内皮细胞(HUVECs),构建H/R模型,并通过转染siRNA与过表达质粒调控CITED2表达。实验分为对照(control)组、H/R组、H/R+OE-NC组、H/R+OE-CITED2组、H/R+siNC组和H/R+siCITED2组。用二氢乙锭(DHE)和JC-1染色检测细胞内ROS水平及线粒体膜电位变化,RT-qPCR和Western blot检测相关基因及蛋白表达。结果与对照组相比,CSF患者血清中TNF-α、IL-6和ROS水平显著升高,PBMCs中HIF-1α和DRP1表达上调,CITED2、SIRT1和MFN2表达下调(P＜0.05)。在HUVECs中,H/R处理后HIF-1α、DRP1表达显著升高,CITED2、SIRT1和MFN2表达降低;过表达CITED2可显著抑制HIF-1α、DRP1表达,上调SIRT1和MFN2,减少ROS生成并恢复线粒体膜电位;敲降CITED2则加剧上述损伤效应。结论 CITED2可通过调控 HIF-1α、DRP1、SIRT1和MFN2的表达,减少ROS生成、恢复线粒体膜电位,从而改善CSF相关的内皮细胞损伤。

关键词: 冠状动脉慢血流, CITED2, 低氧/复氧损伤, 线粒体功能

Abstract: Objective To explore the role of CBP/p300-interacting transactivator 2 with Glu/Asp rich carboxy-terminal domain 2(CITED2) in patients with coronary slow blood flow (CSF) and its regulatory mechanism on endothelial cell hypoxia-reoxygenation (H/R) injury. Methods Peripheral blood samples were collected from CSF patients and healthy controls. Serum TNF-α, IL-6 and ROS levels were detected by ELISA, and the expressions of CITED2, hypoxia-inducible factor-1 α(HIF-1α), Dynamin-related protein 1(DRP1), Sirtuin 1(SIRT1) and Mitofusin 2(MFN2) in peripheral blood mononuclear cells (PBMCs) were analyzed by RT-qPCR and Western blot. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro to construct an H/R model, and the expression of CITED2 was regulated by transfection of siRNA and overexpression plasmid. The experiment was divided into control group, H/R group, H/R+OE-NC group, H/R+OE-CITED2 group, H/R+siNC group and H/R+siCITED2 group. The intracellular ROS level and mitochondrial membrane potential were detected by DHE and JC-1 staining, and the expression of related genes and proteins was detected by RT-qPCR and Western blot. Results Compared with the control group, the levels of TNF-α, IL-6 and ROS in CSF patients were significantly increased(P＜0.05), the expressions of HIF-1α and DRP1 in PBMCs were upregulated, and the expressions of CITED2, SIRT1 and MFN2 were down-regulated(P＜0.05). In HUVECs, the expression of HIF-1α and DRP1 increased significantly after H/R treatment, while the expression of CITED2, SIRT1 and MFN2 decreased. Overexpression of CITED2 significantly inhibited the expression of HIF-1α and DRP1, upregulate SIRT1 and MFN2, reduce ROS production and restore mitochondrial membrane potential. Knockdown of CITED2 aggravated the above damage effect. Conclusions CITED2 can reduce ROS production and restore mitochondrial membrane potential by regulating the expressions of HIF-1α, DRP1, SIRT1 and MFN2, thus improving the endothelial cell injury associated with CSF.

Key words: coronary slow flow, CITED2, hypoxia-reoxygenation injury, mitochondrial function

中图分类号:

R542.2

孙理华, 时司晏, 王维浩, 杨丽, 张培东. CITED2改善低氧/复氧诱导的人脐静脉内皮细胞线粒体功能[J]. 基础医学与临床, 2026, 46(8): 1109-1116.

SUN Lihua, SHI Siyan, WANG Weihao, YANG Li, ZHANG Peidong. CITED2 improves mitochondrial function in hypoxia/reoxygenation-induced human umbilical vein endothelial cells[J]. Basic & Clinical Medicine, 2026, 46(8): 1109-1116.

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CITED2改善低氧/复氧诱导的人脐静脉内皮细胞线粒体功能

CITED2 improves mitochondrial function in hypoxia/reoxygenation-induced human umbilical vein endothelial cells

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