Dexmedetomidine reduce brain injury induced by lung ischemia/reperfusion in mices through inhibiting excessive endoplasmic reticulum stress response / 中华急诊医学杂志

ABSTRACT

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 tablesham 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 ＜ 0.01),brain tissues had obvious damage in I/R,Atip,DEX and DA groups;compared with I/R,Atip and DA group,brain tissues damage was obvious reduced in DEX group,and the Caspase3 activity,brain cell apoptosis index,the protein levels and mRNA expression of p-JNK,Caspase12,CHOP in DEX group were significantly lower,and GRP78 expression increased significantly (P ＜ 0.01).Comparisons among I/R,Atip and DA groups,there were no significant differences in degree of brain injury,Caspase3 activity,brain cell apoptosis index,the protein levels and mRNA expressions of p-JNK,Caspase12,CHOP (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.