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

Lin Yongwen; Yan Xingyu; Chen Yinhui; Ao Dang; Huang Binglong; Liu Ling; Li Chengyan

doi:10.3760/j.issn.1673-4777.2024.11.011

Abstract：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.