2024 年第 11 期 第 19 卷

转录因子EB介导氧化应激对低氧致肺动脉高压新生大鼠肺血管重塑的影响

The effect of transcription factor EB mediated oxidative stress on pulmonary vascular remodeling in neonatal rats with hypoxia-induced pulmonary hypertension

作者：林永文1闫星羽2陈银慧1敖当1黄炳龙1刘玲1李承燕1

英文作者：Lin Yongwen1 Yan Xingyu2 Chen Yinhui1 Ao Dang1 Huang Binglong1 Liu Ling1 Li Chengyan1  

单位：1广东医科大学附属医院儿童医学中心，湛江524000；2河南省儿童医院呼吸科，郑州451100

英文单位：1Children′s Medical Center Affiliated Hospital of Guangdong Medical University Zhanjiang 524000 China; 2Department of Respiratory Henan Children′s Hospital Zhengzhou 451100 China

关键词：转录因子EB；低氧；肺动脉高压；氧化应激；肺血管重塑

英文关键词：TranscriptionfactorEB;Hypoxia;Pulmonaryhypertension;Oxidativestress;Pulmonaryvascularremodeling

• 摘要：

• 目的 探讨转录因子EB（TFEB）介导氧化应激对低氧致肺动脉高压新生大鼠肺血管重塑的影响。方法 将50只新生24 h内SD大鼠按照随机数字表法分为常氧组和低氧组，每组25只，2组分别在第3、5、7、10、14天选取5只取材。常氧组置于常氧饲养，低氧组在低氧箱中饲养，建立新生大鼠新生儿持续性肺动脉高压模型。观察肺部血管形态及TFEB分布情况；检测血清B型脑钠肽（BNP）及活性氧水平，检测肺组织超氧化物歧化酶2（SOD2）、TFEB的mRNA及蛋白表达。结果 低氧组新生大鼠血管壁较常氧组增厚，血管中膜肌层明显增厚。低氧组TFEB主要表达于平滑肌细胞、肺小动脉内皮细胞及终末细支气管上皮等。低氧组第3、5、7、10、14天TFEB吸光度值均高于常氧组［（0.219±0.003）比（0.203±0.011）、（0.235±0.004）比（0.204±0.007）、（0.254±0.003）比（0.203±0.008）、（0.274±0.005）比（0.203±0.006）、（0.282±0.002）比（0.202±0.006）］（均P＜0.05）。低氧组各时点血清活性氧、BNP水平，以及肺组织TFEB、SOD2 mRNA及蛋白表达均高于常氧组（均P<0.05）。结论 TFEB介导氧化应激加重低氧致肺动脉高压新生大鼠肺血管重塑。

• Objective To investigate the effect of transcription factor EB(TFEB) mediated oxidative stress on pulmonary vascular remodeling in neonatal rats with hypoxia-induced pulmonary hypertension(PPHN). Methods Fifty neonatal SD rats, within 24 h after birth, were divided into normal oxygen group and hypoxia group according to the random number table, with 25 rats in each group.Five rats were selected from the two groups on the 3rd, 5th, 7th, 10th and 14th days, respectively. The normal oxygen group was kept under normal oxygen conditions, while the hypoxia group was kept in a hypoxia chamber, thus establishing a model of persistent pulmonary hypertension of the newborn in neonatal rats. The vascular morphology and distribution of TFEB in the lung tissue were observed; the levels of brain natriuretic peptide (BNP) and active oxygen in the serum were detected, and the mRNA and protein expression of superoxide dismutase 2 (SOD2) and TFEB in the lung tissue were measured. Results In the hypoxic group, the vessel wall of newborn rats was thicker than that of the normal oxygen group, and the muscle layer of the middle layer of the vascular media was markedly thicker. In the hypoxic group, TFEB was mainly expressed in smooth muscle cells, pulmonary artery endothelial cells, and terminal bronchiolar epithelial cells. The absorbance values of TFEB in the hypoxic group on the 3rd, 5th, 7th, 10th and 14th days were all higher than those in the normal oxygen group［（0.219±0.003） vs （0.203±0.011）,（0.235±0.004） vs （0.204±0.007）,（0.254±0.003） vs （0.203±0.008）,（0.274±0.005） vs （0.203±0.006）,（0.282±0.002） vs （0.202±0.006）］(all P<0.05). The levels of active oxygen, BNP, and TFEB, SOD2 mRNA and protein expression in the hypoxia group at various time points were all higher than those in the normal oxygen group (all P<0.05). Conclusion TFEB mediates oxidative stress to aggravate pulmonary vascular remodeling in neonatal rats with hypoxia-induced pulmonary hypertension.