The JAK2/STAT3 pathway is involved in dexmedetomidine-induced myocardial protection in rats undergoing cardiopulmonary bypass

BACKGROUND: Many studies have reported that dexmedetomidine protects organs from ischemia/reperfusion-induced injury. However, the mechanism of this protective effect remains inconclusive. METHODS: Rats were randomly divided into 6 groups (n=8). Rats in the sham group were not subjected to cardiopulmonary bypass (CPB) while rats in the other groups underwent CPB for 2 h. Groups L and H received a low and a high dose of dexmedetomidine, respectively. Rats in group AG490 received 10 mg/kg of the Janus kinase 2 (JAK2) inhibitor, AG490, 30 min before anesthesia. Plasma levels of the inflammatory cytokines, interleukin (IL)-6 and IL-10, were measured by enzyme-linked immunosorbent (ELISA), and the apoptosis rate of myocardial cells, the expression of JAK2 and signal transducer and activator of transcription (STAT)3 mRNA, and the protein expression of JAK2, STAT3, pJAK2, pSTAT3, and caspase-3 were analyzed in myocardial tissues by real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. RESULTS: We observed that, in both group L and group H, the level of IL-6 decreased (P<0.05), and the apoptosis rate of myocardial cells were reduced (P<0.05) compared to those in the CPB group. Moreover, qRT-PCR results revealed that dexmedetomidine administration reduced the expression of JAK2 and STAT3 mRNA (P<0.05); pJAK2 and pSTAT3 (P<0.05) protein levels were also reduced as assessed by western blotting and immunohistochemistry (P<0.05). CONCLUSIONS: Dexmedetomidine treatment reduced CPB-related myocardial injury by inhibiting inflammatory reactions and myocardial apoptosis, and can be a potential therapy in CPB-related surgery.