Effect of dexmedetomidine on autophagy during ischemia-reperfusion injury in isolated rat lungs

Objective To evaluate the effect of dexmedetomidine on autophagy during ischemia-reperfusion(I/R) injury in isolated rat lungs. Methods SPF healthy male Sprague-Dawley rats, weighing 250-320 g, were anesthetized with atropine and pentobarbital sodium, and their lungs were excised to establish the isolated lung perfusion model.Thirty lungs in which isolated lung perfusion models were successfully established were divided into 3 groups(n= 10 each) by a random number table method: control group(C group), lung I/R group(I/R group) and dexmedetomidine group(DEX group). The isolated rat lungs were continuously perfused for 150 min in C group.After 15 min of perfusion, the isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in I/R group.In DEX group, the isolated lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine, and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetomidine.Pulmonary vascular resistance(PVR) and partial pressure of arterial oxygen(PaO2) were recorded at 10 min of perfusion and 15, 45 and 75 min of reperfusion.Lung tissues were collected at 75 min of reperfusion for measurement of lung wet weight(W) and dry weight(D) and for examination of morphological changes of lung tissues(with a light microscope) and autophagic vacuoles of lung cells(under an electron microscope). The W/D ratio and lung injury score were calculated.The expression of mammalian target of rapamycin(mTOR), phosphorylated mTOR(p-mTOR) and microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ) in lung tissues was detected by Western blot. Results Compared with C group, the PVR, W/D ratio and lung injury score were significantly increased, the expression of LC3Ⅱ was up-regulated, and PaO2 was decreased in I/R group and DEX group(P<0.05). Compared with I/R group, the PVR, W/D ratio and lung injury score were significantly decreased, the expression of LC3Ⅱ was down-regulated, PaO2 was increased, and the expression of mTOR and p-mTOR was up-regulated in DEX group(P<0.05). A lot of autophagic vacuoles of lung cells were found in I/R group, and a few autophagic vacuoles of lung cells were observed in DEX group. Conclusion The mechanism by which dexmedetomidine reduces isolated lung I/R injury is related to inhibiting autophagy in rats. Key words: Dexmedetomidine; Autophagy; Reperfusion injury; Lung