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食物中的铁在改善雄性小鼠低氧性肺动脉高压心室重构中的作用

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目的 探究食物中的铁在改善雄性小鼠低氧性肺动脉高压(HPH)心室重构中的作用.方法 将雄性小鼠随机分为常氧对照组(暴露于海拔为2 260 m的环境中)、低氧对照组(暴露于模拟海拔为5 000 m的低压氧舱)、低氧高铁组(暴露于模拟海拔为5 000 m的低压氧舱),每组10只.采用右心导管插入术测量右心室收缩压(RVSP),采用相关公式计算右心室肥厚指数(RVHI),采用HE染色法观察心室组织及肺小动脉的变化并计算血管壁面积占血管总面积的百分比(WA%)和血管壁厚度占血管直径的百分比(WT%),采用Western Blot法测定右心室组织中肉毒碱棕榈酰基转移酶 1(carnitine palmitic acyltransferase,CPT1 A)、铁蛋白(ferritin,FTN)、转铁蛋白受体(transferrin receptor,TFR)、膜转铁蛋白(ferroportin,FPN)含量,采用 UPLC-Orbitrap 质谱系统的非靶向组学分析法对常氧对照组、低氧对照组、低氧高铁组小鼠的心室作组学分析.结果 与常氧对照组比较,低氧对照组的RVSP、RVHI和WA%、WT%均升高(P<0.05);FPN蛋白表达水平降低(P<0.05),TFR、FTN、CPT1A蛋白表达水平无统计学差异;心室肌细胞排列紊乱,纤维化更明显.与低氧对照组比较,低氧高铁组小鼠的RVSP、RVHI和WA%、WT%明显下降(P<0.05),FPN蛋白表达水平升高(P<0.05),TFR、FTN、CPT1A蛋白表达无统计学差异;心室肌纤维化程度减轻.与常氧对照组比较,低氧对照组小鼠右心室组织中绝大部分肉碱衍生物及中、长链脂肪酸代谢水平无明显变化;低氧高铁组中绝大部分肉碱衍生物及中、长链脂肪酸代谢水平降低,尤其是不饱和脂肪酸.结论 可能通过食物中的铁增强心肌脂肪酸氧化能力而改善HPH心室重构.
Effects of iron in food in improving ventricular remodeling in male mice with hypoxic pulmonary hypertension
Objective To investigate the effects of iron in food in improving ventricular remodeling in male mice with hypoxic pulmonary hypertension(HPH).Methods Male mice were randomly divided into a normoxic control group(exposed to an altitude of 2 260 m),a hypoxic control group(exposed to a hypobaric oxygen chamber at a simulated altitude of 5 000 m)and a hypoxic iron-high group(exposed to a hypobaric oxygen chamber a simu-lated altitude of 5 000 m),with 10 mice in each group.Right ventricular systolic pressure(RVSP)was measured by right heart catheterization.Right ventricular hypertrophy index(RVHI)was calculated by using the correlation for-mula.The variations in ventricular tissue and small pulmonary arteries were observed by using HE staining.The percentages of vessel wall area to the total area of the blood vessel(WA%)and the vessel wall thickness to the di-ameter of the blood vessel(WT%)were calculated.Western Blot was adopted to determine the content of carnitine palmitic acyltransferase(CPT1A),ferritin(FTN),transferrin receptor(TFR)and ferroportin(FPN)in the right ven-tricle.The ventricles of mice in the normoxic control group,hypoxic control group and hypoxic iron-high group were analyzed by non-targeted histological analysis using the UPLC-Orbitrap mass spectrometry system.Results Compared with the normoxic control group,RVSP,RVHI,WA%and WT%were elevated in the hypoxic control group(P<0.05);the protein expression level of FPN was reduced(P<0.05),and there was no statistically significant difference in the protein expression levels of TFR,FTN and CPTIA;the arrangement of ventricular myocytes was disorganized and fibrosis was more obvious.Compared with the hypoxic control group,RVSP,RVHI,WA%and WT%in the hypoxic iron-high group were significantly decreased(P<0.05);FPN protein expression levels were in-creased(P<0.05),and there was no statistically difference in TFR,FTN and CPT1A protein expression;ventricular myocardial fibrosis was reduced.Compared with the normoxic control group,there was no significant variation in the vast majority of carnitine derivatives and the metabolic levels of medium and long-chain fatty acids in the right ventricular tissues of mice in the hypoxic control group;the vast majority of carnitine derivatives and the metabolic levels of medium and long-chain fatty acids were reduced in the hypoxic iron-high group,especially unsaturated fatty acids.Conclusions It is possible to improve HPH ventricular remodeling by enhancing myocardial fatty acid oxidation ability through iron in food.

hypoxiapulmonary hypertensionironlipidmetabolism

王慧杰、耿玉梅、李文颖、白振忠

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青海大学,西宁 810016

青海省人民医院 西宁 810007

低氧 肺动脉高压 脂质 代谢

高原医学教育部重点实验室资助项目

2023-KF-2

2024

中国高原医学与生物学杂志
青海大学

中国高原医学与生物学杂志

影响因子:0.266
ISSN:1006-8252
年,卷(期):2024.45(4)