Ischemic post-conditioning can improve lung I/R injury by regulating zinc homeostasis in rats
10.3969/j.issn.1000-4718.2025.11.014
- VernacularTitle:缺血后处理通过调控锌稳态减轻大鼠肺缺血/再灌注损伤
- Author:
Yuan CHENG
1
;
Junpeng XU
;
Man HUANG
;
Sian CHEN
;
Lei YING
;
Shuyuan WANG
;
Dong SONG
;
Wantie WANG
Author Information
1. 温州医科大学基础医学院缺血/再灌注损伤研究所,浙江 温州 325035
- Publication Type:Journal Article
- Keywords:
zinc homeostasis;
PI3K/AKT signaling pathway;
apoptosis;
ischemic post-conditioning;
isch-emia/reperfusion injury
- From:
Chinese Journal of Pathophysiology
2025;41(11):2191-2199
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aimed to investigate the effect of ischemic post-conditioning(I-post-C)on lung ischemia-reperfusion injury(LIRI)in rats and relationship between I-post-C and zinc homeostasis.METHODS:SPF SD rats(6～8 weeks old)were randomly divided into four groups,with eight rats in each group:control group,ischemia/reper-fusion(I/R)group,I-post-C group and I-post-C+zinc ion chelator TPEN group.Inductively coupled plasma mass spec-trometry(ICP-MS)was used to measure the concentration of zinc ions in lung tissues.HE staining,lung wet/dry weight ra-tio(W/D),total lung water content(TLW),and index of quantitative assessment(IQA)of lung injury were used to detect the degree of lung tissue injury in each group.Mitochondrial membrane potential was measured using extraction and JC-1 mitochondrial membrane potential detection kits.TUNEL assay was used to detect the level of apoptosis in lung tissues.Western blot was used to detect the protein expression levels of caspase-3,solute carrier family 39 member 8(SLC39A8/ZIP8),solute carrier family 30 member 9(SLC30A9/ZNT9),and PI3K/AKT/GSK-3β in lung tissues of each group.RT-qPCR was used to detect ZIP8 and ZNT9.RESULTS:Compared to the control group,the I/R group showed significantly aggravated lung tissue injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced cell apoptosis(P<0.05),re-duced mitochondrial membrane potential(P<0.01),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved caspase-3/pro-caspase-3 ratio(P<0.01),and reduced ZIP8 expression(P<0.05).Compared to the I/R group,the I-post-C group exhibited alleviated injury(P<0.05 or P<0.01),increased zinc ion levels(P<0.01),reduced apoptosis(P<0.01),restored mitochondrial membrane potential(P<0.01),elevated PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),decreased cleaved caspase-3/pro-caspase-3 ratio(P<0.05),and in-creased ZIP8 expression(P<0.05).Compared to the I-post-C group,the I-post-C+TPEN group demonstrated aggravated injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced apoptosis(P<0.01),reduced mitochondrial membrane potential(P<0.05),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved cas-pase-3/pro-caspase-3 ratio(P<0.05),and reduced ZIP8 expression(P<0.05).ZNT9 expression showed no significant differences among the groups(P>0.05).CONCLUSION:Ischemic postconditioning can improve LIRI by regulating zinc homeostasis,activating PI3K/AKT signaling pathway,inactivating glycogen synthase kinase 3β,inhibiting the de-cline of mitochondrial membrane potential,and antagonizing cell apoptosis in rats.
