Recombinant Schistosoma japonicum cystatin alleviates acute liver injury in mice by inhibiting endoplasmic reticulum stress,inflammation and hepatocyte apoptosis
10.12122/j.issn.1673-4254.2024.06.13
- VernacularTitle:重组日本血吸虫半胱氨酸蛋白酶抑制剂对急性肝损伤小鼠的保护作用及机制
- Author:
Lingjun LU
1
;
Xiaodi YANG
;
Huaping ZHANG
;
Yuan LIANG
;
Xiulan SHI
;
Xin ZHOU
Author Information
1. 山西医科大学病理生理教研室,山西 太原 030002
- Keywords:
acute liver injury;
Schistosoma japonicum cystatin;
endoplasmic reticulum stress;
inflammatory response;
apoptosis
- From:
Journal of Southern Medical University
2024;44(6):1126-1134
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.
