目的 探讨miR⁃146b⁃5p在高氧诱导的新生大鼠支气管肺发育不良相关肺动脉高压（bronchopulmonary dysplasia⁃associated pulmonary hypertension, BPD⁃PH）肺血管重塑中的作用及机制。 方法 选取32只Sprague⁃Dawley新生大鼠，随机分为常氧组、BPD⁃PH组、过表达组和抑制剂组，每组8只。常氧组于21%氧浓度环境中饲养，其余3组置于85.0%±0.5%的高氧箱中构建BPD⁃PH模型。其中过表达组经尾静脉注射腺病毒ADV1⁃miR⁃146b⁃5p，抑制剂组注射miR‑146b‑5p抑制剂。建模14 d后，采用共聚焦显微镜观察腺病毒在肺组织中的转染效率；采用直接测压法测定右心室收缩压（right ventricular systolic pressure, RVSP），分离右心室组织称重并计算右心室肥厚指数（right ventricular hypertrophy index, RVHI）；苏木精-伊红染色观察肺血管形态并计算血管中膜厚度百分比（medial thickness percentage, MT%）、血管中膜面积百分比（medial area percentage, MA%）；透射电子显微镜观察肺血管内皮细胞线粒体的超微结构；3,3'⁃二氨基联苯胺普鲁士蓝染色和亚铁离子试剂盒检测肺组织铁沉积水平；实时荧光定量PCR检测核因子E2相关因子2（nuclear factor erythroid 2⁃related factor 2, Nrf2）、谷胱甘肽过氧化物酶4（glutathione peroxidase 4, GPX4）、溶质载体家族7成员11（solute carrier family 7 member 11, SLC7A11）、长链酰基辅酶A合成酶4（acyl⁃CoA synthetase long⁃chain family member 4, ACSL4）mRNA表达水平，免疫印迹法检测Nrf2、GPX4、SLC7A11、ACSL4蛋白表达水平。 结果 与常氧组比较，BPD⁃PH组新生大鼠RVSP升高，RVHI、MT%、MA%增大，线粒体肿胀，铁沉积增多，Nrf2、GPX4、SLC7A11 mRNA及蛋白表达下调，ACSL4 mRNA及蛋白表达上调（P0.05）。与BPD‑PH组比较，过表达组新生大鼠RVSP升高，RVHI、MT%、MA%增大，线粒体重度肿胀，铁沉积明显增多，Nrf2、GPX4、SLC7A11 mRNA及蛋白表达下调，ACSL4 mRNA及蛋白表达上调（P0.05）；抑制剂组RVSP降低，RVHI、MT%、MA%减小，线粒体肿胀缓解，铁沉积减少，Nrf2、GPX4、SLC7A11 mRNA及蛋白表达上调，ACSL4 mRNA及蛋白表达下调（P0.05）。 结论 在高氧暴露下，miR⁃146b⁃5p过表达可促进新生大鼠肺血管重塑，其机制可能与抑制Nrf2/GPX4信号通路、调控铁死亡有关。

Objective To investigate the role and mechanism of miR-146b-5p in pulmonary vascular remodeling in neonatal rats with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) induced by hyperoxia. Methods Thirty-two Sprague-Dawley neonatal rats were randomly assigned to normoxia group, BPD-PH group, overexpression group, and inhibitor group (n=8 per group). The normoxia group was raised in 21% oxygen, while the other groups were exposed to 85.0%±0.5% hyperoxia to induce BPD-PH. The overexpression group received tail vein injection of ADV1-miR-146b-5p adenovirus; the inhibitor group received miR-146b-5p inhibitor injections. After 14 days, adenovirus transfection efficiency in lung tissue was confirmed by confocal microscopy. Right ventricular systolic pressure (RVSP) was measured by direct manometry. Right ventricular hypertrophy index (RVHI) was calculated by weighing isolated ventricular tissues. Hematoxylin-eosin staining was used to assess pulmonary vascular morphology, and medial thickness percentage (MT%) and medial area percentage (MA%) of pulmonary vessels were calculated. Mitochondrial ultrastructure of pulmonary vascular endothelial cells was observed by transmission electron microscopy (TEM). Iron deposition in lung tissue was detected by DAB Prussian blue staining and ferrous ion colorimetric assay. Quantitative real-time PCR was used to measure mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4). Protein expression levels of these molecules were detected by Western blotting. Results Compared with the normoxia group, the BPD-PH group showed significantly increased RVSP, RVHI, MT%, and MA% (P0.05), swollen mitochondria, increased iron deposition, downregulated mRNA and protein expression of Nrf2, GPX4, and SLC7A11, and upregulated expression of ACSL4 (P0.05). Compared with the BPD-PH group, the overexpression group exhibited further increases in RVSP, RVHI, MT%, and MA%, severe mitochondrial swelling, significantly elevated iron deposition, decreased Nrf2, GPX4, and SLC7A11 mRNA and protein levels, and increased ACSL4 expression (P0.05). In contrast, the inhibitor group demonstrated decreased RVSP, RVHI, MT%, and MA%, alleviated mitochondrial swelling, reduced iron deposition, upregulated mRNA and protein levels of Nrf2, GPX4, and SLC7A11, and downregulated mRNA and protein levels of ACSL4 (P0.05). Conclusions Overexpression of miR-146b-5p promotes pulmonary vascular remodeling in neonatal rats exposed to hyperoxia, likely through inhibition of the Nrf2/GPX4 signaling pathway and regulation of ferroptosis.