Dexmedetomidine reduce brain injury induced by lung ischemia/reperfusion in mices through inhibiting excessive endoplasmic reticulum stress response

Objective To investigate the effect of dexmedetomidine(DEX) on the reduction of brain injury induced by lung ischemia/reperfusion(I/R) in mices through inhibiting excessive endoplasmic reticulum stress response(ERS). Methods Fifty healthy SPF male C57BL/6J mices, weighing 20-24 g, aged 8-10 weeks, were divided into 5 groups (n=10 each) using a random number table: sham operation group(sham group), lung ischemia/reperfusion group(I/R group), atipamezole goup(Atip group), dexmedetomidine group(DEX group), dexmedetomidine plus atipamezole group(DA group). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by reperfusion for 180 min. In Atip, DEX and DA groups, atipamezole 250 μg/kg, dexmedetomidine 20 μg/kg and dexmedetomidine 20 μg/kg plus atipamezole 250 μg/kg were injected intraperitoneally, respectively, at 30 min before modeling, other procedures were as the same as the I/R group. At 180 min of reperfusion, the animals were sacrificed and the brain tissues were harvested for the observation of morphological changes. The Caspase-3 activity and the apoptosis index of the brain cells were also determined. The levels of protein and mRNA expression of p-JNK, Caspase-12, CHOP and GRP78 in brain tissues were detected by Western blot and RT-PCR. The datas were analyzed using SPSS 19.0 software and multiple-group comparisons were performed using one-way ANOVA, and P<0.05 for the difference was statistically significant. Results Compared with the sham group, the Caspase3 activity and brain cell apoptosis index, the protein levels and mRNA expressions of p-JNK, Caspase12, CHOP, GRP78 were significantly increased(P 0.05), while the expression of GRP78 in DA group was significantly increased (P<0.01). Conclusion DEX can effectively relieve the brain injury induced by lung I/R in mice, which may be associated with stimulation of α2 adrenergic receptor and inhibition of excessive endoplasmic reticulum stress response and reducing brain cell apoptosis. Key words: Dexmedetomidine; Ischemia/reperfusion injury; Mice; Brain; Endoplasmic reticulum stress; Cell apoptosis; Caspase3