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  

Effects of iron in food in improving ventricular remodeling in male mice with hypoxic pulmonary hypertension

作　　者：王慧杰 耿玉梅 李文颖 白振忠[1] WANG Huijie;GENG Yumei;LI Wenying;BAI Zhenzhong(Qinghai University,Xining 810016,China;Qinghai Provincial People's Hospital,Xining 810007,China)

机构地区：[1]青海大学,西宁810016 [2]青海省人民医院,西宁810007

出　　处：《中国高原医学与生物学杂志》2024年第4期255-262,270,共9页Journal of Chinese High Altitude Medicine & Biology

基　　金：高原医学教育部重点实验室资助项目(编号:2023-KF-2)。

摘　　要：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2260 m的环境中)、低氧对照组(暴露于模拟海拔为5000 m的低压氧舱)、低氧高铁组(暴露于模拟海拔为5000 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,CPT1A)、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。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 2260 m),a hypoxic control group(exposed to a hypobaric oxygen chamber at a simulated altitude of 5000 m)and a hypoxic iron-high group(exposed to a hypobaric oxygen chamber a simulated altitude of 5000 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 formula.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 wallthickness to the diameter 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 ventricle.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 CPT1A;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 increased(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 th

关 键 词：低氧 肺动脉高压 铁 脂质 代谢 

分 类 号：R34[医药卫生—基础医学]