Effect of sevoflurane on hepatic ischemia-reperfusion injury in rats via JAK2-STAT3 pathway

L.-J. Sima, X.-W. Ma

Department of Anesthesiology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang City, Henan Province, China. klim59785@gmail.com

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• Pharmacology

OBJECTIVE: To investigate the effect of sevoflurane on hepatic ischemia-reperfusion injury in rats via janus kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) pathway.

MATERIALS AND METHODS: Forty healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n=10), model group (HIRI group, n=10), sevoflurane intervention group (SF group, n=10), and sevoflurane combined with AG490 intervention group (AG490 group, n=10). Liver and serum samples were collected after reperfusion for 6 h. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α were detected by enzyme-linked immunosorbent assay (ELISA). JAK2, STAT3, p-JAK2 and p-STAT3 were detected by Western-blot. The expression level of cobalt quenching technique was used to detect the permeability of mitochondrial membrane permeability transition pore (mPTP).

RESULTS: The levels of ALT, AST, AKP, IL-1β, IL-6 and TNF-α in HIRI group were higher than those in sham group (p < 0.05), those in SF group were lower than those in HIRI group (p < 0.05), while those in AG490 group were higher than those in SF group (p < 0.05). The levels of JAK2 protein, pJAK2 protein, STAT3 protein and P STAT3 protein in HIRI group were lower than those in sham group (p < 0.05); the levels of each protein in SF group were higher than those in HIRI group (p < 0.05), while those in AG490 group were lower than those in SF group (p < 0.05). The open degree of HIRI group was higher than that of sham group (p < 0.05); SF group was lower than that of HIRI group, and AG490 group was higher than that of SF group (p < 0.05).

CONCLUSIONS: Sevoflurane can significantly improve HIRI and reduce hepatic immune inflammation in rats. The mechanism may be related to activating JAK2-STAT3 pathway and inhibiting the overopening of mPTP.

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