Schistosoma japonicum cystatin has protective effects against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
10.12122/j.issn.1673-4254.2025.01.14
- Author:
Wenjuan DUO
1
;
Yixiang WANG
1
;
Jiaxing WANG
1
;
Xinlong XU
1
;
Linxian LI
1
;
Dongchen YANG
1
;
Qili SHEN
2
;
Lichun YANG
2
;
Xiaojing LIU
1
;
Qiwang JING
1
;
Liang CHU
2
;
Xiaodi YANG
1
Author Information
1. School of Basic Medical Sciences, Bengbu Medical University, Bengbu 233030, China.
2. Department of General Surgery, Second Affiliated Hospital of Bengbu Medical University, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
Schistosoma japonicum cysteine protease inhibitors;
cecal ligation and puncture;
immunoregulatory cytokines;
lipopolysaccharide;
sepsis
- MeSH:
Animals;
Mice;
Sepsis/drug therapy*;
Male;
Schistosoma japonicum/chemistry*;
Mice, Inbred C57BL;
Cystatins/therapeutic use*;
Interleukin-10/metabolism*;
Interleukin-6/blood*;
Tumor Necrosis Factor-alpha/blood*;
Disease Models, Animal;
Transforming Growth Factor beta/metabolism*
- From:
Journal of Southern Medical University
2025;45(1):110-117
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis.
METHODS:Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3+CD4+CD25+Foxp3+ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival.
RESULTS:The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment.
CONCLUSIONS:rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
