The Role of Dexmedetomidine in Hepatic Ischemia-Reperfusion Injury Via a Nitric Oxide-Dependent Mechanism in Rats

초록

Background. Dexmedetomidine is known to protect against ischemia-reperfusion (IR) in various organs; however, the mechanisms of dexmedetomidine in the liver remain unclear. We investigated whether dexmedetomidine preconditioning leads to hepatic protection and whether nitric oxide was associated with this protective mechanism by employing N-nitro-L-arginine methyl ester (L-NAME), a nitrous oxide synthase inhibitor. Methods. Experiment 1 included 24 rats in 4 groups: sham, IR, 30 mu g/kg of dexmedetomidine, and 50 mu g/kg of dexmedetomidine. Experiment 2 included 36 rats in 6 groups: IR, 50 mu g/kg of dexmedetomidine, 10 mg/kg of L-NAME, 10 mg/kg of L-NAME + 50 mu g/kg of dexmedetomidine, 30 of mg/kg L-NAME, and 30 mg/kg of L-NAME + 50 mu g/kg of dexmedetomidine. All drugs were administered intraperitoneally. The levels of serum transaminases, malondialdehyde, superoxide dismutase, tumor necrosis factor-alpha, nuclear factor-kappa B, and c-Jun N-terminal kinase were measured 6 hours after hepatic surgery. Results. Dexmedetomidine demonstrated a dose-dependent decrease in serum transaminase levels. The 50-mu g/kg dexmedetomidine group showed a significant decrease in malondialdehyde levels (P =.002), increase in superoxide dismutase levels (P =.002), and a significantly lower level of phosphorylated tumor necrosis factor-alpha, nuclear factor-kappa B, and c-Jun N-terminal kinase (P =.002, respectively) compared with the IR injury group. These protective effects of dexmedetomidine were partially reversed by pretreatment with L-NAME (P <.01 for 20 and 30 mg/kg of L-NAME). Conclusion. In hepatic IR injury, dexmedetomidine might protect the liver via antioxidative and anti-inflammatory responses, and nitric oxide production could play a role in these protective mechanisms.

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