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].

作者信息

Xie Ou, Li Shan-Shan, Luo Yang, Wang Le

机构信息

Department of Neonatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2024 Jul 15;26(7):757-764. doi: 10.7499/j.issn.1008-8830.2401078.

DOI:10.7499/j.issn.1008-8830.2401078

PMID:39014954

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11562046/

Abstract

OBJECTIVES

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 (240 μg/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-1α and PCNA mRNA levels.

RESULTS

Compared to the normoxia group, the hypoxia and hypoxia + 2ME groups showed increased RVSP and upregulated HIF-1α and PCNA protein and mRNA expression levels at 3, 7, 14, and 21 days after hypoxia (<0.05). Furthermore, at 7, 14, and 21 days after hypoxia, the hypoxia group showed increased MT% and MA% (<0.05). In comparison to the hypoxia group, the hypoxia + 2ME group exhibited reduced RVSP and downregulated HIF-1α and PCNA protein and mRNA expression levels, along with decreased MT% and MA% at 7, 14, and 21 days after hypoxia (<0.05).

CONCLUSIONS

2ME may protect against HPH in neonatal rats by inhibiting the expression of HIF-1α and PCNA and reducing pulmonary vascular remodeling. .

摘要

目的

研究2-甲氧基雌二醇（2ME）对新生大鼠缺氧性肺动脉高压（HPH）的保护作用。

方法

将96只Wistar新生大鼠随机分为常氧组、缺氧组和缺氧+2ME组，每组再分为3天、7天、14天和21天亚组，每组8只。缺氧组和缺氧+2ME组分别每日皮下注射生理盐水和2ME（240μg/kg），常氧组饲养于常氧环境，每日注射生理盐水。采用直接测压法测量右心室收缩压（RVSP）。用苏木精-伊红染色评估肺血管形态，指标包括小肺动脉中膜厚度相对于外径的百分比（MT%）和小肺动脉中膜横截面积相对于总横截面积的百分比（MA%）。采用免疫组织化学法检测缺氧诱导因子-1α（HIF-1α）和增殖细胞核抗原（PCNA）蛋白的表达水平，采用实时定量PCR评估HIF-1α和PCNA mRNA水平。

结果

与常氧组相比，缺氧组和缺氧+2ME组在缺氧后3天、7天、14天和21天RVSP升高，HIF-1α和PCNA蛋白及mRNA表达水平上调（<0.05）。此外，缺氧后7天、14天和21天，缺氧组MT%和MA%升高（<0.05）。与缺氧组相比，缺氧+2ME组在缺氧后7天、14天和21天RVSP降低，HIF-1α和PCNA蛋白及mRNA表达水平下调，MT%和MA%降低（<0.05）。