Protective effects of 2-methoxyestradiol against hypoxic pulmonary hypertension in neonatal rats
10.7499/j.issn.1008-8830.2401078
- VernacularTitle: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
- Author:
Ou XIE
1
;
Shan-Shan LI
;
Yang LUO
;
Le WANG
Author Information
1. 新疆医科大学儿科学院,新疆乌鲁木齐 830054
- Keywords:
Hypoxic pulmonary hypertension;
2-Methoxyestradiol;
Hypoxia-inducible factor-1α;
Neonatal rat
- From:
Chinese Journal of Contemporary Pediatrics
2024;26(7):757-764
- CountryChina
- Language:Chinese
-
Abstract:
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(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(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-1α and 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-1α and PCNA and reducing pulmonary vascular remodeling.
