학술논문
Salidroside protects against intestinal barrier dysfunction in septic mice by regulating IL-17 to block the NF-[kappa]B and p38 MAPK signaling pathways
Document Type
Report
Author
Source
Experimental and Therapeutic Medicine. February 2023, Vol. 25 Issue 2
Subject
Language
English
ISSN
1792-0981
Abstract
Introduction Sepsis can be secondary to severe trauma, burn, infection and other clinical acute and critical diseases, manifested as systemic inflammatory response disorder and host autoimmune injury and can result [...]
Sepsis is a systemic inflammatory response syndrome, mainly caused by infection or suspected infectious factors. The intestine is not only one of the most easily involved organs in the course of sepsis, but also the dynamic organ for the course of sepsis. The present study investigated the protective effect and mechanism of salidroside on intestinal barrier dysfunction of septic mice. Briefly, C57BL/6 mice were used to establish a septic model and then administered with salidroside. The ileum tissues of mice were examined by histopathological examination. Fluorescein isothiocyanate-dextran concentration was measured. IL-17, IL-6, IL-13 and TNF-[alpha] levels in ileum tissues and NF-[kappa]B and p38 MAPK activations were detected by ELISA and the expressions of NF-[kappa]B p65 and p38 MAPK protein with their phosphorylation and intestinal tight junction proteins were gauged by western blotting. The above assays were performed again to investigate the effect of anti-IL-17A and salidroside (160 mg/kg) alone or in combination. The septic model induced the ileum tissue injury, increased intestinal permeability and TNF-[alpha], IL-17 and IL-6 levels, activated NF-[kappa]B and p38 MAPK pathways, promoted the expressions of NF-[kappa]B p65 and p38 MAPK and their phosphorylation, while suppressing the levels of IL-13 and intestinal tight junction proteins. Salidroside and anti-IL-17A partially reversed the above effects of septic model, which in combination further strengthened the reversing effect. Collectively, salidroside protected against intestinal barrier dysfunction in septic mice by downregulating IL-17 level to inhibit NF-[kappa]B and p38 MAPK signaling pathways, thus providing a new treatment direction. Key words: sepsis, salidroside, IL-17, NF-[kappa]B signaling pathway, p38 mitogen-activated protein kinase signaling pathway
Sepsis is a systemic inflammatory response syndrome, mainly caused by infection or suspected infectious factors. The intestine is not only one of the most easily involved organs in the course of sepsis, but also the dynamic organ for the course of sepsis. The present study investigated the protective effect and mechanism of salidroside on intestinal barrier dysfunction of septic mice. Briefly, C57BL/6 mice were used to establish a septic model and then administered with salidroside. The ileum tissues of mice were examined by histopathological examination. Fluorescein isothiocyanate-dextran concentration was measured. IL-17, IL-6, IL-13 and TNF-[alpha] levels in ileum tissues and NF-[kappa]B and p38 MAPK activations were detected by ELISA and the expressions of NF-[kappa]B p65 and p38 MAPK protein with their phosphorylation and intestinal tight junction proteins were gauged by western blotting. The above assays were performed again to investigate the effect of anti-IL-17A and salidroside (160 mg/kg) alone or in combination. The septic model induced the ileum tissue injury, increased intestinal permeability and TNF-[alpha], IL-17 and IL-6 levels, activated NF-[kappa]B and p38 MAPK pathways, promoted the expressions of NF-[kappa]B p65 and p38 MAPK and their phosphorylation, while suppressing the levels of IL-13 and intestinal tight junction proteins. Salidroside and anti-IL-17A partially reversed the above effects of septic model, which in combination further strengthened the reversing effect. Collectively, salidroside protected against intestinal barrier dysfunction in septic mice by downregulating IL-17 level to inhibit NF-[kappa]B and p38 MAPK signaling pathways, thus providing a new treatment direction. Key words: sepsis, salidroside, IL-17, NF-[kappa]B signaling pathway, p38 mitogen-activated protein kinase signaling pathway