2-甲氧基雌二醇对新生大鼠缺氧性肺动脉高压的保护作用  

Protective effects of 2-methoxyestradiol against hypoxic pulmonary hypertension in neonatal rats

作　　者：谢鸥 李珊珊 罗洋 王乐[2] XIE Ou;LI Shan-Shan;LUO Yang;WANG Le(Department of Neonatology,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学儿科学院,新疆乌鲁木齐830054 [2]新疆医科大学第一附属医院新生儿科,新疆乌鲁木齐830054

出　　处：《中国当代儿科杂志》2024年第7期757-764,共8页Chinese Journal of Contemporary Pediatrics

基　　金：国家自然科学基金(82060287)。

摘　　要：目的探讨2-甲氧基雌二醇(2-methoxyestradiol,2ME)在新生大鼠缺氧性肺动脉高压中的保护作用。方法96只Wistar新生大鼠随机分为常氧组、缺氧组和缺氧+2ME组,每组随机分为3 d、7 d、14 d、21 d亚组,每个亚组8只。缺氧组和缺氧+2ME组分别予以每日皮下注射生理盐水和2ME(剂量240μg/kg),常氧组在常氧环境下饲养,每日皮下注射生理盐水。直接测压法测量右心室收缩压(right ventricular systolic pressure,RVSP);苏木精-伊红染色观察肺血管形态,计算肺血管重塑指标肺小动脉中层血管壁厚度占血管外径的百分比(MT%)和肺小动脉中层截面积占血管总截面积的百分比(MA%);免疫组化法检测肺组织中缺氧诱导因子-1α(hypoxiainducible factor-1α,HIF-1α)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白表达水平;实时荧光定量聚合酶链反应检测HIF-1α、PCNA mRNA表达水平。结果与常氧组比较,缺氧3、7、14、21 d时缺氧组、缺氧+2ME组RVSP升高,HIF-1α、PCNA蛋白和mRNA表达水平上调(P<0.05),缺氧7、14、21 d时缺氧组MT%、MA%增加(P<0.05);与缺氧组比较,缺氧3、7、14、21 d时缺氧+2ME组RVSP降低,HIF-1α、PCNA蛋白和PCNA mRNA表达水平下调(P<0.05),缺氧7、14、21 d时缺氧+2ME组MT%、MA%减少(P<0.05)。结论2ME可能通过抑制HIF-1α、PCNA表达,减轻肺血管重塑,对新生大鼠缺氧性肺动脉高压发挥保护作用。Objective To investigate the protective effects of 2-methoxyestradiol(2ME)against hypoxic pulmonary hypertension(HPH)in neonatal rats.Methods Ninety-six Wistar neonatal rats were randomly divided into a normoxia group,a hypoxia group,and a hypoxia+2ME group,with each group further subdivided into 3-day,7-day,14-day,and 21-day subgroups,containing eight rats each.The hypoxia and hypoxia+2ME groups received daily subcutaneous injections of saline and 2ME(240μg/kg),respectively,while the normoxia group was raised in a normoxic environment with daily saline injections.Right ventricular systolic pressure(RVSP)was measured using the direct pressure method.Pulmonary vascular morphology was assessed using hematoxylin and eosin staining,with metrics including the percentage of medial thickness of small pulmonary arteries relative to the external diameter(MT%)and the cross-sectional area of the media of small pulmonary arteries relative to the total cross-sectional area(MA%).Immunohistochemistry was used to detect the expression levels of hypoxia-inducible factor-1α(HIF-1α)and proliferating cell nuclear antigen(PCNA)proteins,while real-time quantitative PCR was used to to assess HIF-1αand PCNA mRNA levels.Results Compared to the normoxia group,the hypoxia and hypoxia+2ME groups showed increased RVSP and upregulated HIF-1αand PCNA protein and mRNA expression levels at 3,7,14,and 21 days after hypoxia(P<0.05).Furthermore,at 7,14,and 21 days after hypoxia,the hypoxia group showed increased MT%and MA%(P<0.05).In comparison to the hypoxia group,the hypoxia+2ME group exhibited reduced RVSP and downregulated HIF-1αand PCNA protein and mRNA expression levels,along with decreased MT%and MA%at 7,14,and 21 days after hypoxia(P<0.05).Conclusions 2ME may protect against HPH in neonatal rats by inhibiting the expression of HIF-1αand PCNA and reducing pulmonary vascular remodeling.

关 键 词：缺氧性肺动脉高压 2-甲氧基雌二醇 缺氧诱导因子-1Α 新生大鼠 

分 类 号：R722.1[医药卫生—儿科]