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新生儿持续性肺动脉高压(PPHN)是新生儿常见的肺部疾病,死亡率高。血管密度降低和肺血管阻力(PVR)增加是PPHN的主要原因。目前研究表明内皮型一氧化氮合酶(eNOS)损伤及一氧化氮形成减少在PPHN的发展过程中发挥重要作用。胎羊宫内未闭动脉导管结扎是最常用的研究PPHN病理生理机制的动物模型。对PPHN胎羊肺动脉内皮细胞(PAEC)的研究显示,PPHN时eNOS解耦联、四氢生物蝶呤(BH4)生成减少及烟酰胺腺嘌呤二核苷酸(NADPH)氧化酶(NOX)活性增高,导致活性氧簇生成增加。活性氧族生成增加不仅使一氧化氮生物活性降低,而且增加PAEC细胞凋亡和自噬,导致血管生成受损。补充BH4,抗氧化治疗和增加锰超氧化物歧化酶(MnSOD)表达可以使eNOS复耦联,增加血管生成。研究结果表明,PPHNPAEC表型变化包含多种信号通路。动物实验揭示了几种PPHN的潜在治疗方法。
Neonatal Persistent Pulmonary Hypertension (PPHN) is a common neonatal pulmonary disease with high mortality. Decreased vascular density and increased pulmonary vascular resistance (PVR) are the main causes of PPHN. The current studies show that endothelial nitric oxide synthase (eNOS) injury and nitric oxide formation decreased PPHN play an important role in the development process. Intrauterine intrauterine patent ductus arteriosus ligation is the most commonly used animal model of PPHN pathophysiology. Studies on PPHN fetal sheep pulmonary artery endothelial cells (PAECs) showed that eNOS decoupling, reduction of tetrahydrobiopterin (BH4) formation, and increased nicotinamide adenine dinucleotide (NADPH) oxidase (NOX) activity during PPHN , Leading to increased generation of reactive oxygen species. Increased production of reactive oxygen species not only reduces the biological activity of nitric oxide, but also increases apoptosis and autophagy in PAEC cells, leading to impaired angiogenesis. Supplementation of BH4, anti-oxidative treatment and increased manganese superoxide dismutase (MnSOD) expression can couple eNOS to increase angiogenesis. The results show that, PPHNPAEC phenotypic changes include a variety of signaling pathways. Animal experiments revealed several potential treatments for PPHN.