中国比较医学杂志2025，Vol.35Issue(9)：37-49,13.DOI:10.3969/j.issn.1671-7856.2025.09.004
常压低氧与低压低氧诱导肺动脉高压大鼠模型的比较研究
Comparative study of rat models of pulmonary hypertension induced by normobaric hypoxia and hypobaric oxygen
摘要
Abstract
Objective To evaluate pulmonary vascular remodeling,right ventricular function,intestinal barrier integrity,and inflammatory factor expression in rat models of pulmonary hypertension(PH)induced by normobaric hypoxia(NH)and hypobaric hypoxia(HH).We also aimed to compare modeling method and establish an experimental basis for understanding the pathogenesis of PH and for developing appropriate treatment strategies.Methods From June 2024 to December 2024,eighteen 6-week-old male SPF Sprague-Dawley rats were assigned randomly to three groups:normobaric normoxia(Control),NH,and HH groups.Mean pulmonary artery pressure(mPAP)was measured by right heart catheterization.Right ventricular function was assessed using echocardiography and right ventricular hypertrophy index(RVHI).Pulmonary vascular remodeling and intestinal mucosal barrier damage were evaluated via hematoxylin/eosin staining.Colon permeability was quantified by colon ligation followed by fluorescein isothiocyanate-dextran injection.Expression levels of inflammatory factors in lung and colon tissues were analyzed by enzyme-linked immunosorbent assays.Results Right heart function assessment revealed that mPAP was significantly increased(P＜0.05),pulmonary artery acceleration time(PAAT)was shortened,and RVHI and right ventricular free wall thickness(RVFW)were significantly elevated(P＜0.05)in rats in NH and HH groups compared with Control group.Rats in NH group demonstrated a prolonged pulmonary ejection time(PET)and reduced PAAT/PET ratio compared with HH group,indicating more pronounced right heart dysfunction.Pulmonary vascular morphology demonstrated that percentage of medial area percentage(MA％)and percentage of wall thickness percentage(WT％)of pulmonary vessels were significantly higher in NH and HH groups compared with Control group(P＜0.05).Moreover,MA％was markedly increased in the NH group relative to the HH group(P＜0.05),suggesting more severe pulmonary vascular remodeling in NH group.Regarding intestinal injury,rats in NH and HH groups exhibited shorter colon length,increased mucosal damage,and significantly increased permeability compared with Control group(P＜0.05),while rats in HH group showed more prominent inflammatory cell infiltration compared with NH group,confirming intestinal mucosal barrier damage in both groups.In terms of inflammation,expression levels of interleukin(IL)6,IL1β,and IL 17a were significantly elevated in lung and colon tissues from rats in NH and HH groups compared with Control group(P＜0.05).Notably,expression levels of IL6 and IL1 β in lung tissue and IL17a in colon tissue were significantly higher in NH group compared with HH group(P＜0.05),while IL6 expression in colon tissue was relatively lower(P＜0.05),indicating local inflammation in lung and colon tissues in both groups.Conclusions There are phenotypic differences between PH rat models induced by NH and HH,with respect to pulmonary vascular remodeling,right heart function,intestinal mucosal barrier injury,and the expression of inflammatory factors in lung and intestinal tissues.These result demonstrate that air pressure contributes to the pathogenesis and progression of PH.Different air pressures may affect the development of PH via distinct mechanisms,thereby offering critical insights into the pathological changes of PH,potential therapeutic strategies to mitigate disease progression,and the elucidation of inflammatory mechanisms underlying PH based on the lung-intestine axis.关键词
肺动脉高压/低压低氧/常压低氧/肠黏膜屏障损伤/肺血管重构/右心功能/炎症Key words
pulmonary arterial hypertension/hypobaric hypoxia/normobaric hypoxia/intestinal mucosal barrier injury/pulmonary vascular remodeling/right ventricular function/inflammation分类
医药卫生引用本文复制引用
李寒雪,孙进连,郑丁瑜,刘瑞欣,华玉美多,马燕..常压低氧与低压低氧诱导肺动脉高压大鼠模型的比较研究[J].中国比较医学杂志,2025,35(9):37-49,13.基金项目
国家自然科学基金(32260222) （32260222）
青海省2025年基础研究计划项目(2025-ZJ-748) （2025-ZJ-748）
青海大学青年科研基金项目(2023-QYY-4). （2023-QYY-4）
