Effects of Sirt1 on macrophage apoptosis in Vibrio vulnificus sepsis
10.7644/j.issn.1674-9960.2024.08.007
- VernacularTitle:Sirt1对创伤弧菌脓毒症中巨噬细胞凋亡的影响及机制
- Author:
Huinan ZHOU
1
,
2
;
Chenglin WU
;
Jianfei LIU
;
Chen ZHANG
;
Lijun ZHOU
;
Kewei QIN
Author Information
1. 南方医科大学第二临床学院,广州 510515
2. 解放军总医院第六医学中心,中心实验室,北京 100048
- Keywords:
Vibrio vulnificus;
resveratrol;
poly ADP-ribose polymerase;
caspase-3;
Sirt1;
apoptosis;
macrophage
- From:
Military Medical Sciences
2024;48(8):601-607
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of silencing regulatory protein 1(Sirt1)in the regulation of Vibrio vulnificus sepsis-induced macrophage apoptosis and the molecular mechanisms.Methods Mouse RAW264.7 macrophages which stably overexpressed Sirt1 were constructed and screened by genistein G418.CCK-8 analysis was used to detect the proliferation of cells in the control group and Sirt1-Flag group.The changes of expression levels of apoptosis-associated protein poly ADP-ribose polymerase(PARP),cleaved-PARP,caspase3,cleaved-caspase3 and acetylated p53 in different treatment groups were detected via Western blotting.A Vibrio vulnificus sepsis model in mice was established,and the expression levels of apoptosis-associated protein cleaved-caspase3 in the lung,spleen and liver of mice of different treatment groups were detected by immunohistochemistry.Results Overexpression of Sirt1 reduced VVC-induced RAW264.7 cell damage.Overexpression of Sirt1 as well as RSV pretreatment lowered the expression of apoptosis-associated protein cleaved-PARP,cleaved-caspase3 and acetylated p53 in VVC-stimulated RAW264.7 cells and mouse peritoneal macrophages.In the mouse model of Vibrio vulnificus sepsis,therapeutic administration of RSV reduced the expression of apoptosis-associated protein marker cleaved-caspase3 in lung,spleen and liver tissues.Conclusion Sirt1 can inhibit p53 acetylation and reduces apoptosis in mouse macrophages,which helps protect against Vibrio vulnificus sepsis.