成纤维细胞生长因子19通过激活核因子E2相关因子2/血红素加氧酶-1信号通路减轻血管内皮细胞的炎性损伤
[FGF19 alleviates inflammatory injury in vascular endothelial cells by activating the Nrf2/HO-1 signaling pathway].
作者信息
Zhang Yan-Jun, Xiao Fei-Fei, Li Xiao-Hua, Tang Shen-Hua, Sang Yi, Liu Chao-Yue, Li Jian-Chang
机构信息
Department of Pediatrics, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, China.
出版信息
Zhongguo Dang Dai Er Ke Za Zhi. 2025 May 15;27(5):601-608. doi: 10.7499/j.issn.1008-8830.2411076.
OBJECTIVES
To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG).
METHODS
Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the gene.
RESULTS
Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (<0.05).
CONCLUSIONS
FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
目的
探讨成纤维细胞生长因子（FGF）19在高糖（HG）诱导的血管内皮细胞炎症损伤中的作用及机制。
方法
人脐静脉内皮细胞（HUVECs）随机分为四组：对照组、HG组、FGF19组和HG + FGF19组（每组n = 3）。采用CCK8法评估不同浓度葡萄糖和/或FGF19对HUVEC活力的影响。利用流式细胞术检测FGF19对HUVEC凋亡的影响。通过ELISA检测白细胞介素-6（IL-6）、诱导型一氧化氮合酶（iNOS）、总超氧化物歧化酶（T-SOD）和丙二醛（MDA）水平。采用实时定量PCR和蛋白质印迹法测定血管内皮生长因子（VEGF）、核因子红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的mRNA和蛋白质表达水平。细胞进一步分为对照组、siRNA-Nrf2（siNrf2）组、HG组、HG + FGF19组、HG + FGF19 +阴性对照组和HG + FGF19 + siNrf2组（每组n = 3），以观察沉默该基因后FGF19对高糖诱导的HUVEC氧化应激损伤的影响。
结果
与对照组相比，HG组凋亡率升高，IL-6、iNOS和MDA水平升高，VEGF mRNA和蛋白质表达增加，T-SOD活性降低，Nrf2和HO-1的mRNA和蛋白质表达降低（P < 0.05）。与HG组相比，HG + FGF19组凋亡率降低，IL-6、iNOS和MDA水平降低，VEGF mRNA和蛋白质表达降低，T-SOD活性增加，Nrf2和HO-1的mRNA和蛋白质表达增加（P < 0.05）。与HG + FGF19 +阴性对照组相比，HG + FGF19 + siNrf2组T-SOD活性降低，MDA水平升高（P < 0.05）。
结论
FGF19可能通过Nrf2/HO-1信号通路减轻HG诱导的血管内皮细胞炎症损伤。
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