Dexmedetomidine-induced cardioprotection in a mouse model of lung ischemia-reperfusion: the relationship with endoplasmic reticulum stress

Abstract

Objective To evaluate dexmedetomidine-induced cardioprotection in a mouse model of lung ischemia-reperfusion(I/R)and the relationship with endoplasmic reticulum stress. Methods Forty healthy SPF male C57BL/6J mice, weighing 20-24 g, aged 8-10 weeks, were divided into 4 groups(n=10 each)using a random number table: sham operation group(Sham group), lung I/R group(I/R group), dexmedetomidine group(Dex group)and dexmedetomidine plus atipamezole(specific α2-adrenergic receptor antagonist)group(DA group). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion.In group Sham, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min.In Dex and DA groups, dexmedetomidine 20 μg/kg and dexmedetomidine 20 μg/kg plus atipamezole 250 μg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model.At 180 min of reperfusion, blood samples were collected from the orbit for determination of creatine kinase-MB(CK-MB)and lactic dehydrogenase(LDH)activities in serum.The animals were then sacrificed, and hearts were removed for determination of apoptosis in cardiomyocytes(by TUNEL)and expression of phosphorylated c-Jun N-terminal kinase(p-JNK), caspase-12, CCAAT/enhancer-binding protein homologous protein(CHOP)and glucose-regulated protein 78(GRP78)in myocardial tissues(by Western blot), and expression of JNK, caspase-12, CHOP, GRP78 mRNA in myocardial tissues(by real-time polymerase chain reaction). Apoptosis index was calculated. Results Compared with Sham group, the serum CK-MB and LDH activities and apoptosis index were significantly increased, the expression of p-JNK, JNK mRNA, and caspase-12, CHOP and GRP78 protein and mRNA was up-regulated in I/R, Dex and DA groups(P 0.05). Compared with DEX group, the serum CK-MB and LDH activities and apoptosis index were significantly increased, the expression of p-JNK, JNK mRNA, and caspase-12 and CHOP protein and mRNA was up-regulated(P 0.05). Conclusion Dexmedetomidine can reduce myocardial injury induced by lung I/R, and the mechanism may be related to activation of α2-adrenergic receptors and inhibition of endoplasmic reticulum stress in myocardial cells of mice. Key words: Dexmedetomidine; Lung; Reperfusion injury; Myocardium; Endoplasmic reticulum; Stress