Protective Effects of Ischemic Postconditioning on Livers in Rats with Limb Ischemia-Reperfusion via Glycogen Synthase Kinase 3 beta (GSK-3ß)/Fyn/Nuclear Receptor-Erythroid-2-Related Factor (Nrf2) Pathway.
Med Sci Monit
; 26: e923049, 2020 Jul 20.
Article
en En
| MEDLINE
| ID: mdl-32686659
ABSTRACT
BACKGROUND Ischemia/reperfusion (I/R) injury not only exists in ischemic tissues and organs, but also can cause damage to distant tissues and organs. As the largest metabolic organ of the human body, the liver is very vulnerable to injury after limb I/R. However, the mechanism of liver injury caused by limb I/R injury has not been fully elucidated. This study investigated the effect and mechanism of ischemic postconditioning (IPO) on the liver after hindlimb I/R in rats. MATERIAL AND METHODS A rat model of hindlimb I/R was established and treated by IPO. Liver function, changes of oxidative stress index and inflammation, Bcl-2 and Bax proteins, and apoptosis were assessed. The structural changes were observed by electron microscopy. GSK-3ß/Fyn/Nrf2 levels were detected by quantitative PCR and Western blot. RESULTS IPO significantly reduced serum AST, ALP, LDH, and ALT levels induced by I/R. Compared with the I/R group, the levels of SOD, GSH-Px, and CAT in the IPO group were significantly increased, while the levels of MDA, MPO, and ROS were significantly decreased. The IPO group had significantly higher Bcl-2 level and significantly lower Bax level compared to the I/R group. Consistently, IPO decreased the apoptosis rate induced by I/R. Furthermore, IPO lowered the levels of TNF-alpha, IL-1ß, IL-10, and INF-γ and alleviated the ultrastructural changes of hepatocytes. Finally, Nrf2, Fyn, and GSK-3ß mRNA and protein levels in the IPO group were significantly higher than in the I/R group. CONCLUSIONS IPO protects against liver injury caused by I/R injury of the hindlimb, possibly via the GSK-3ß/Fyn/Nrf2 pathway.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
Poscondicionamiento Isquémico
/
Hígado
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Med Sci Monit
Asunto de la revista:
MEDICINA
Año:
2020
Tipo del documento:
Article