Effect of dexmedetomidine pretreatment on apoptosis in hippocampal neurons of rats undergoing one-lung ventilation / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmnedetomidine pretreatment on apoptosis in hippocampal neurons of rats undergoing one-lung ventilation (OLV).Methods Ninety adult male SpragueDawley rats,aged 10-11 months,weighing 260-300 g,were divided into 3 groups (n=30 each) using a random number tabletwo-lung ventilation (TLV) group,group OLV and dexmedetomidine pretreatment group (group D).Dexmedetomidine 25 μg/kg was injected intraperitoneally at 45 min before OLV in group D.After tracheal intubation,the animals were ventilated in volume-controlled mode.OLV was performed for 90 mnin followed by 30 min of TLV in OLV and D groups.TLV was performed for 120 min in group TLV.On 1,3 and 7 days after ventilation,6 rats in each group were selected,and Morris water maze test was carried out to evaluate the cognitive function.The swimming speed,time of staying at the target quadrant,and frequency of crossing the platform quadrant were recorded.Six rats in each group were selected immediately after ventilation and sacrificed,the hippocampi were removed for detection of cell apoptosis,and the apoptosis index was calculated.Immediately after ventilation and on 1,3 and 7 days after ventilation,6 rats in each group were selected and sacrificed,and the hippocampi were removed for determination of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2),phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB),Bcl-2 and Bax expression.The ratio of Bcl-2 expression to Bax expression (Bcl-2/Bax ratio) was calculated.Results Compared with group TLV,the time of staying at the target quadrant was significantly shortened,the frequency of crossing the platform quadrant was decreased,the apoptosis index was increased,the expression of pERK1,pERK2,pCREB and Bcl-2 was down-regulated,the expression of Bax was up-regulated,and Bcl-2/Bax ratio was decreased in group OLV (P＜0.05 or 0.01).Compared with group OLV,the time of staying at the target quadrant was significantly prolonged,the frequency of crossing the platform quadrant was increased,the apoptosis index was decreased,the expression of pERK1,pERK2,pCREB and Bcl-2 was up-regulated,the expression of Bax was down-regulated,and Bcl-2/Bax ratio was increased in group D (P＜0.05 or 0.01).Conclusion Dexmedetomidine pretreatment decreases apoptosis in hippocampal neurons through activating ERK/CREB signaling pathway,thus reducing cognitive dysfunction of rats undergoing OLV.