Effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia-reperfusion in rats: an in vitro experiment

Abstract

Objective To investigate the effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia-reperfusion(I/R)in rats. Methods Thirty lungs, which were isolated from SPF adult male Sprageue-Dawley rats, in which the model of isolated lung perfusion was successfully established, were divided into 3 groups(n=10 each)using a random number table: sham operation group(S group), I/R group and dexmedetomidine group(D group). The lungs were subjected to 60 min of ischemia and apnea after 15-min ischemia followed by 75 min of reperfusion and ventilation to establish the model of isolated lung I/R injury.In group D, the lungs were perfused with K-H solution containing 10 nmol/L dexmedetomidine for 15 min and then subjected to 60 min of ischemia and apnea followed by ventilation and reperfusion with K-H sloution containing 10 nmol/L dexmedetomidine for 75 min.Airway resistance, lung compliance, perfusion flow and partial pressure of arterial oxygen(PaO2)were recorded at 10 min of perfusion(T0)and 15, 45 and 75 min after restoration of perfusion(T1-3). Lung tissues were obtained at 75 min after restoration of perfusion for determination of wet/dry weight ratio(W/D ratio)and for examination of pathological changes and ultrastructure of lungs.The activity of superoxide dismutase(SOD)and content of malondialdehyde(MDA)in lung tissues were measured by improved pyrogallol autoxidation method and thiobarbituric acid method, respectively.The expression of β-endorphin and interleukin-8(IL-8)in lung tissues was detected by Western blot. Results Compared with group S, the airway resistance was significantly increased, and the lung compliance, perfusion flow and PaO2 were decreased during the perfusion restoration period, the W/D ratio and content of MDA were increased, the activity of SOD was decreased, and the expression of β-endorphin and IL-8 was up-regulated in I/R and D groups(P<0.05). Compared with group I/R, the airway resistance was significantly decreased, and the lung compliance, perfusion flow and PaO2 were increased during the perfusion restoration period, the W/D ratio and content of MDA were decreased, the activity of SOD was increased, the expression of β-endorphin and IL-8 was down-regulated(P<0.05), and the pathological changes of lungs were significantly attenuated in group D. Conclusion The mechanism by which dexmedetomidine reduces lung I/R injury may be related to inhibiting lipid peroxidation and inflammatory response of lung tissues in rats. Key words: Dexmedetomidine; Inflammation; Lipid peroxidation; Reperfusion injury; Lung