Mechanism of Sab in sexual dimorphism of acute liver injury in mice
10.3969/j.issn.1671-8348.2025.03.002
- VernacularTitle:Sab在性别差异性急性肝损伤小鼠中的作用机制研究
- Author:
Xiaoda JIANG
1
;
Xu HUANG
;
Jun ZHANG
Author Information
1. 武汉大学人民医院消化内科/消化系统疾病湖北省重点实验室,武汉 430060
- Keywords:
liver injury;
acetaminophen;
sex differences;
Sab
- From:
Chongqing Medicine
2025;54(3):567-572
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of SH3 domain binding protein(Sab)in sex-differ-ential acute liver injury in mice.Methods Female and male mice were randomly divided into control group,acetaminophen(APAP)-induced acute liver injury group,Ad-Sab group,estrogen receptor antagonist group and estrogen receptor agonist group.After corresponding treatments,liver tissues and serum were collected for ALT/AST detection,hematoxylin-eosin(HE)staining and Western blot analysis.Results In the APAP-induced acute liver injury group,male mice showed significantly higher p-JNK activity in hepatic cytoplasm and mitochondria than female mice(P＜0.05).Male mice had lower Sab expression levels than female mice(P＜0.05).In the Ad-Sab group,male mice injected with Ad-Sab showed more severe hepatic injury,higher Sab expression and elevated ALT levels compared with Ad-lacZ injected male mice(P＜0.05).In the estrogen receptor antagonist group,fulvestrant-treated females showed dose-dependent increases in Sab expression.Fe-male mice treated with Ad-Sab plus fulvestrant showed more severe liver injury and higher ALT levels than those receiving Ad-lacZ plus fulvestrant after 4 h of 200 mg/kg APAP administration exhibited more severe liver injury and higher ALT levels than controls(P＜0.05).PPT-protected males in the estrogen receptor ag-onist group showed reduced hepatic damage and lower ALT levels compared with control male mice(P＜0.05).Conclusion Sab expression level determines the severity of JNK-dependent acute drug-induced liver injury.Fe-male mice have lower hepatic Sab protein expression levels and exhibit significant resistance to liver injury.
