摘要目的 评价右美托咪定预先给药对单肺通气大鼠海马神经元凋亡的影响.方法 成年雄性SD大鼠90只,10～11月龄,体重260～ 300 g,采用随机数字表法,将其分为3组(n=30):双肺通气组(TLV组)、单肺通气组(OLV组)和右美托咪定预先给药组(D组).D组于单肺通气前45min腹腔注射右美托咪定25 μg/kg.气管插管术后行容量控制通气,OLV组与D组行单肺通气90min,然后行双肺通气30 min,TLV组行双肺通气120 min.每组分别于机械通气后1、3、7d时取6只大鼠,行Morris水迷宫实验,记录游泳速度、目标象限停留时间和穿越平台次数,以评价认知功能;每组于机械通气后即刻取6只大鼠,取海马,测定细胞凋亡情况,计算细胞凋亡指数;每组于机械通气后即刻、1、3、7d时取6只大鼠,取海马,测定磷酸化细胞外调节蛋白激酶1/2(pERK1/2)、磷酸化环磷腺苷效应元件结合蛋白(pCREB)、Bcl-2和Bax的表达,并计算Bcl-2表达与Bax表达的比值(Bcl-2/Bax比值).结果 与TLV组比较,OLV组目标象限停留时间缩短,穿越平台次数减少,海马细胞凋亡指数升高,海马pERK1、pERK2、pCREB和Bcl-2表达下调,Bax表达上调,Bcl-2/Bax比值降低(P＜0.05或0.01);与OLV组比较,D组目标象限停留时间延长,穿越平台次数增加,海马细胞凋亡指数降低,海马pERK 1/2、pCREB和Bcl-2表达上调,Bax表达下调,Bcl-2/Bax比值升高(P＜0.05或0.01).结论 右美托咪定预先给药可通过激活ERK/CREB信号通路降低单肺通气大鼠海马神经元凋亡,从而减轻认知功能障碍.

abstractsObjective 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 table:two-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.