Effects of SIRT2 on liver tight junctions and endoplasmic reticulum stress in cold-treated mice
10.16303/j.cnki.1005-4545.2025.07.15
- VernacularTitle:SIRT2对冷处理后小鼠肝脏组织紧密连接及内质网应激的影响
- Author:
Tianrui ZHAO
1
;
Linlin XUE
;
Junshu NIE
;
Huaixiu ZHANG
;
Chenchen LI
;
Jingru GUO
Author Information
1. 黑龙江八一农垦大学动物科技学院,黑龙江大庆 163319
- Publication Type:Journal Article
- Keywords:
SIRT2;
liver;
cold treatment;
tight junctions;
endoplasmic reticulum stress;
mice
- From:
Chinese Journal of Veterinary Science
2025;45(7):1469-1477
- CountryChina
- Language:Chinese
-
Abstract:
In order to investigate the effect of SIRT2 on tight junctions and endoplasmic reticulum stress in liver tissues of cold-treated mice,10 each of 5-week-old male C57BL/6 mice and SIRT2 knockout mice were selected and randomly divided into the wild-type room-temperature control group(WT Control),the wild-type cold-treated group(WT Cold),the SIRT2 knockout+room-temperature control group(KO Control)and SIRT2 knockout+cold treatment group(KO Cold).Mice in the room-temperature control group were kept at a temperature of(24+2)℃,and the cold-treatment group was placed in a(4+2)℃ artificial climate chamber for 3 h of random stimu-lation per day for 3 weeks.H&E staining,Masson staining,and transmission electron microscopy were employed to examine the microscopic and ultrastructural changes in mouse liver;AST and ALT concentrations in mouse serum were detected by biochemical analyzers;Western blot analysis was used to detect the expressions of tight junction-related proteins(Claudin1,Occludin),endo-plasmic reticulum stress-related proteins(GRP78,CHOP,XBP1,p-eIF2α,eIF2α),and pro-inflam-matory cytokines(TNF-α,IL-1β,IL-6).The results showed that compared with WT Control,the liver lobular structure of WT Cold and KO Control mice was unclear,hepatic cord arrangement was disordered,cytoplasm was loose,white vacuoles appeared,a small amount of collagen deposi-tion and fibroplasia,mitochondria were slightly swollen in hepatocytes,and endoplasmic reticulum was unevenly distributed,while the serum concentrations of AST and ALT were increased(P＜0.050,P＜0.010),and the liver tissues showed decreased protein expression of Occludin and Clau-din1(P＜0.050,P＜0.010,P＜0.001),and increased protein expression of GRP78,CHOP,XBP1,p-eIF2α/eIF2α,TNF-α,IL-6,and IL-1β(P＜0.050,P＜0.010,P＜0.001);compared with the KO Control,KO Cold mice showed a large number of white vacuoles,a small number of balloon-like lesions,inflammatory cell infiltration,obvious collagen deposition and fibroplasia,mitochondrial swelling in hepatocytes,mitochondrial ridge reduction,endoplasmic reticulum thickening,and ser-um AST and ALT concentrations increased(P＜0.010),and in liver tissue,the protein expression of Occludin and Claudinl decreased(P＜0.010),while the protein expression of GRP78,CHOP,XBP1,p-eIF2α/eIF2α,TNF-α,IL-6 and IL-1β increased(P＜0.050,P＜0.010,P＜0.001).The re-sults showed that SIRT2 knockdown could aggravate the liver tissue tight junction damage caused by cold treatment,induce endoplasmic reticulum stress,and further promotes the inflammatory re-sponse.
