Effects Of Dexmedetomidine On Mitochondrial Damage Induced By Ischemia-reperfusion In Isolated Rat Lungs

Objective To investigate the effects of different doses of dexmedetomidine(Dex)on ischemia/reperfusion injury in a rat ex vivo lung model.Methods Sprague-Dawley rats were randomly divided into six groups(n = 6 each):control group(group C),ischemia-reperfusion group(group IR),yohimbine group(group Y),low-dose dexmedetomidine group(group D₁),high-dose dexmedetomidine group(group D₁₀)and high-dose dexmedetomidine plus yohimbine group(group DY).An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury.Drugs were added to the perfusion solution for reperfusion.Lung injury was assessed by histopathological changes,airway pressure(Raw),lung compliance(Cdyn),perfusion flow(V_T),pulmonary venous oxygen partial pressure(PaO₂),lung wet/dry(W/D)weight ratio and the activity of LDH.Results At the moment of T₀,there were no significant differences in the values of lung function parameters.There was no difference in the pulmonary function indexes of group IR and group Y.From the moment of T₁,compared with group C,V_T,Cdyn and PaO₂ of the remaining groups showed a downward trend,and Raw showed an upward trend(P < 0.05).From the moment of T₂,compared with group IR,V_T,Cdyn,and PaO₂ of group D₁ and group D₁₀ were significantly increased,and Raw was significantly reduced(P < 0.05).From the moment of T₃,compared with group D₁,Raw of group D₁₀ was significantly reduced(P < 0.05).Compared with group D₁₀,the pulmonary function of group DY decreased significantly(P < 0.05).There was no statistical difference between group IR and group Y in W/D ratio.Compared with group C,different degrees of pulmonary edema occurred in the other groups(P < 0.05).Compared with group IR,the W/D values of group D₁ and group D₁₀ were significantly reduced(P < 0.05).There was no statistical difference in W/D values between group D₁ and group D₁₀.Compared with group D₁₀,W/D ratio of group DY increases(P < 0.05).Compared with group C,the pulmonary alveolar structures of group IR,group Y and group DY were destroyed,ruptured and collapsed,the pulmonary stromal edema widened,and a large number of inflammatory cells penetrated.Compared with group IR,the alveolar structure of group D₁ and group D₁₀ was relatively complete,and the degree of pulmonary septal hyperemia and inflammatory cell infiltration was significantly reduced.Compared with group C,LDH activity of group IR,group Y and group DY increased(P < 0.05).Compared with group IR,LDH activity of group D₁ and group D₁₀ decreased(P < 0.05).Compared with group D₁,LDH activity of group D₁₀ decreased(P < 0.05).Compared with group D₁ and D₁₀,LDH activity of group DY increased(P < 0.05).Conclusion Dexmedetomidine can alleviate lung ischemia-reperfusion injury in a rat ex vivo lung model,and yohminbine can turn down the effect.Objective To evaluate the effects of dexmedetomidine on ischemia /reperfusion-induced mitochondrial injury in a rat ex vivo lung model.Methods Sprague-Dawley rats were randomly divided into four groups(n = 6 each):control group(group C),ischemia-reperfusion group(group IR),high-dose dexmedetomidine group(group D₁₀)and high-dose dexmedetomidine plus yohimbine group(group DY).An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury.Drugs were added to the perfusion solution for reperfusion.The levels of superoxide dismutase(SOD),malondialdehyde(MDA),reactive oxygen species(ROS),and adenosine triphosphate(ATP)were measured.Mitochondrial swelling and mitochondrial membrane potential(MMP)were measured.Quantitative analysis of Cytochrome C was made in cytosol and mitochondria after LIRI.Lung tissue TUNEL staining was made and apoptosis index was measured after LIRI.Result Compared with group C,the content of MDA in group IR and group DY increased,SOD activity decreased,and ROS content in group IR,group D₁₀,and group DY increased(P<0.05).Compared with group IR,the MDA content of group D₁₀ decreased,SOD activity increased,and the ROS content of group D₁₀ and group DY decreased(P<0.05).Compared with group D₁₀,the content of MDA and ROS in group DY increased and SOD activity decreased(P<0.05).Compared with group C,the absorption of group IR,group D₁₀,and group DY increased,MMP decreased,and ATP generation decreased(P<0.05).Compared with group IR,absorption of group D₁₀ decreased,ATP generation increased significantly,and MMP increased(P<0.05).Compared with group D₁₀,group DY increased the absorption change and ATP generation decreased(P<0.05).Compared with group C,the content of Cyt C cytoplasm in group IR was significantly higher than that in mitochondria(P<0.05).Compared with group IR,Cyt C released from mitochondria into cytoplasm in group D₁₀ significantly reduced(P<0.05).Compared with group D₁₀,the content of Cyt C in group DY cytoplasm increased significantly(P<0.05).Compared with group C,the number of positive apoptosis cells in lung tissue section of group IR,D₁₀ and DY increased,and the apoptosis index increased(P<0.05).Compared with IR group,the number of positive apoptosis cells in group D₁₀ decreased significantly and the apoptosis index decreased(P<0.05).Compared with group D₁₀,the number of positive apoptosis cells in group DY increased and the apoptosis index increased(P<0.05).Conclusion Dexmedetomidine can alleviate lung ischemia-reperfusion injury in a rat ex vivo lung model,and the mechanism may be related to alleviating mitochondrial injury and oxidative stress.