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
- VernacularTitle:重组日本血吸虫半胱氨酸蛋白酶抑制剂可通过调节炎症微环境对"二次打击"脓毒症小鼠发挥治疗作用
- Author:
Wenjuan DUO
1
;
Yixiang WANG
;
Jiaxing WANG
;
Xinlong XU
;
Linxian LI
;
Dongchen YANG
;
Qili SHEN
;
Lichun YANG
;
Xiaojing LIU
;
Qiwang JING
;
Liang CHU
;
Xiaodi YANG
Author Information
1. 蚌埠医科大学基础医学院,安徽 蚌埠 233030;安徽省感染与免疫重点实验室,安徽 蚌埠 233030;南京紫金医院,江苏南京 210000
- Publication Type:Journal Article
- Keywords:
Schistosoma japonicum cysteine protease inhibitors;
lipopolysaccharide;
cecal ligation and puncture;
sepsis;
immunoregulatory cytokines
- From:
Journal of Southern Medical University
2025;45(1):110-117
- CountryChina
- Language:Chinese
-
Abstract:
Objective 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.Conclusion rSj-Cystatin has a protective effect against"two-hit"sepsis in mice by regulating the inflammatory microenvironment.
