Sevoflurane Postconditioning Reduces Apoptosis by Activating the JAK-STAT Pathway After Transient Global Cerebral Ischemia in Rats

Abstract

Objective: The antiapoptotic effects of sevoflurane postconditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats. Methods: Forty-five rats were randomly assigned to five groups: sham (n=5), control (10 min of ischemia, n=10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n=10), AG490 (a JAK2 selective inhibitor, intravenous administration of 40 mg kg-1 before ischemia, n=10), and sevoflurane postconditioning plus AG490 group (n=10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated three days after ischemia. Results: The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490 and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all five groups. P-JAK2, P-STAT3 and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490 and sevoflurane postconditioning plus AG490 groups. Conclusions: Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.