HIF-1α/HO-1/VEGF-A信号通路在自体动静脉内瘘成熟不良中的调控机制

Regulatory mechanism of HIF-1α/HO-1/VEGF-A signaling pathway in immaturity of autogenous arteriovenous fistula

  • 摘要:
    目的 观察慢性肾脏病5期、行自体动静脉内瘘(AVF)患者在内瘘不同成熟结局条件下低氧诱导因子-1α/血红素加氧酶-1/血管内皮生长因子A(HIF-1α/HO-1/VEGF-A)信号通路的表达水平差异,探讨HIF-1α/HO-1/VEGF-A信号通路在AVF成熟过程中的调控机制。
    方法 选取慢性肾脏病5期、拟行AVF手术的45例患者作为研究对象,在内瘘手术过程中采集血管标本,依据术后8周内瘘成熟结局分为AVF成熟组(n=35)和AVF成熟不良组(n=10)。采用逆转录-聚合酶链反应(RT-PCR)检测HIF-1α/HO-1/VEGF-A信号通路HIF-1αHO-1VEGF-A的基因表达水平; 采用蛋白免疫印迹法检测HIF-1α、HO-1、VEGF-A的蛋白表达水平; 采用酶联免疫吸附测定(ELISA)检测下游炎症因子如白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)、转化生长因子-β(TGF-β)表达水平。
    结果 AVF成熟组HIF-1α mRNA、HO-1 mRNA、VEGF-A mRNA表达水平高于AVF成熟不良组,差异有统计学意义(P < 0.01); AVF成熟组HIF-1α、HO-1、VEGF-A蛋白表达水平高于AVF成熟不良组,差异有统计学意义(P < 0.01); AVF成熟组IL-1β、IL-8、TGF-β表达水平低于AVF成熟不良组,差异有统计学意义(P < 0.01)。
    结论 HIF-1α/HO-1/VEGF-A信号通路表达水平的上调有利于内瘘的早期成熟。HIF-1α/HO-1/VEGF-A信号通路表达水平的测定对AVF的早期成熟结局有一定的预测意义。

     

    Abstract:
    Objective To observe the differences in the expression levels of the hypoxia-inducible factor-1α/heme oxygenase-1/vascular endothelial growth factor A (HIF-1α/HO-1/VEGF-A) signaling pathway under different maturation outcomes of arteriovenous fistula (AVF) in patients with stage 5 chronic kidney disease, and explore the regulatory mechanism of the HIF-1α/HO-1/VEGF-A signaling pathway in the maturation process of AVF.
    Methods A total of 45 patients with AVF surgery for stage 5 chronic kidney disease were selected as research objects, vascular specimens were collected during the AVF surgery, and the patients were divided into AVF maturation group (n=35) and AVF poor maturation group (n=10) based on the AVF maturation outcomes within 8 weeks after surgery. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression levels of HIF-1α, HO-1 and VEGF-A in the HIF-1α/HO-1/VEGF-A signaling pathway; the Western blotting was used to detect the protein expression levels of HIF-1α, HO-1 and VEGF-A; the enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of downstream inflammatory factors such as interleukin-1β (IL-1β), interleukin-8 (IL-8), and transforming growth factor-β (TGF-β).
    Results The expression levels of HIF-1α mRNA, HO-1 mRNA, and VEGF-A mRNA in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the protein expression levels of HIF-1α, HO-1 and VEGF-A in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the expression levels of IL-1β, IL-8 and TGF-β in the AVF maturation group were significantly lower than those in the AVF poor maturation group (P < 0.01).
    Conclusion The upregulation of the HIF-1α/HO-1/VEGF-A signaling pathway is conducive to the early maturation of AVF. The measurement of the expression levels of the HIF-1α/HO-1/VEGF-A signaling pathway has a certain predictive significance for the early maturation outcome of AVF.

     

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