右美托咪定对体外循环大鼠肺缺血再灌注损伤时细胞凋亡的影响

Effect of dexmedetomidine on cell apoptosis during lung ischemia-reperfusion injury in a rat model of cardiopulmonary bypass

目的评价右美托咪定对体外循环大鼠肺缺血再灌注损伤时细胞凋亡的影响。方法SPF级健康成年雄性SD大鼠96只,体重350~500 g,采用随机数字表法分为4组(n=24):假手术组(S组)、CPB组(C组)、CPB+左肺缺血再灌注组(IR组)和CPB+左肺缺血再灌注+右美托咪定组(D组)。S组仅开胸,不行CPB;C组仅建立CPB模型;IR组在建立CPB模型基础上,制备左肺缺血再灌注损伤模型;D组建立CPB+左肺缺血再灌注模型,并经尾静脉泵注3μg/kg右美托咪定10 min后,继续以1.5μg·kg^-1·h^-1的速率泵注右美托咪定至术毕。分别于术前(T0)、开放左肺门后10 min(T1)和术毕(T2)时各组随机取8只大鼠取左侧肺组织,光镜观察肺组织病理学结果,并行病理损伤评分;TUNEL法检测肺组织细胞凋亡情况,并进行免疫组化评分(IHS)。结果与S组比较,其余3组T1,2时肺组织病理损伤评分、IHS和细胞凋亡指数升高(P<0.05);与C组比较,IR组和D组T1,2时肺组织病理损伤评分、IHS和细胞凋亡指数升高(P<0.05);与IR组比较,D组T2时肺组织病理损伤评分、IHS和细胞凋亡指数降低(P<0.05)。结论右美托咪定减轻CPB大鼠肺缺血再灌注损伤的机制与抑制细胞凋亡有关。

Objective To evaluate the effect of dexmedetomidine on cell apoptosis during lung ischemia-reperfusion(I/R)injury in a rat model of cardiopulmonary bypass(CPB).Methods Ninety-six SPF healthy adult male Sprague-Dawley rats,weighing 350-500 g,were divided into 4 groups(n=24 each)using a random number table method:sham operation group(group S),CPB group(group C),CPB plus left lung I/R group(group IR),and CPB plus left lung I/R plus dexmedetomidine group(group D).The chest was only opened,and the rats underwent no CPB in group S.Only the CPB model was established in group C.The model of left lung I/R injury was established based on the CPB model in group IR.In group D,the model of CPB plus left pulmonary I/R injury was established,dexmedetomidine was intravenously infused in a dose of 3μg/kg through the tail vein,followed by a continuous infusion of 1.5μg·kg^-1·h^-1 until the end of surgery.Eight rats were selected in each group before operation(T0),at 10 min after opening the left hilum(T1),and at the end of operation(T2),the left lung tissues were taken for examination of pathological changes(with a light microscope)which were scored and for determination of cell apoptosis,and immunohistochemistry score(IHS)was assessed.The apoptosis index was calculated.Results Compared with group S,the pathological changes of lung tissues,IHS and apoptosis index were significantly increased at T1,2 in the other three groups(P<0.05).Compared with group C,the pathological changes of lung tissues,IHS and apoptosis index were significantly increased at T1,2 in IR and D groups(P<0.05).Compared with group IR,the pathological changes of lung tissues,IHS and apoptosis index were significantly decreased at T2 in group D(P<0.05).Conclusion The mechanism by which dexmedetomidine reduces lung I/R injury during CPB is related to inhibiting cell apoptosis in rats.