Mechanisms of the soluble guanylate cyclase stimulator sGC003 for improving high altitude pulmonary edema in mice
10.3867/j.issn.1000-3002.2025.08328
- VernacularTitle:可溶性鸟苷酸环化酶刺激剂sGC003改善小鼠高原肺水肿作用及机制
- Author:
Yulong HUANG
1
;
Shuo LI
;
Yingxian SHI
;
Guixin SU
;
Jinshui ZHANG
;
Zhibing ZHENG
;
Yun DENG
;
Youzhi ZHANG
Author Information
1. 安徽理工大学第一附属医院,安徽 淮南 232007;军事医学研究院,北京 100850;安徽理工大学医学院,安徽淮南 232001
- Publication Type:Journal Article
- Keywords:
soluble guanylate cyclase;
sGC003;
high altitude pulmonary edema;
vasodilator-stim-ulated phosphoprotein;
lung injury
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(10):761-769
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.
