U50488H对体外循环术后大鼠认知功能与海马细胞凋亡影响

Effect of U50488H on cognitive function and hippocampal cell apoptosis induced by CPB in rats

目的探讨κ-阿片受体激动剂U50488H对体外循环术后大鼠认知功能与海马细胞凋亡的影响。方法选取清洁级成年雄性SD大鼠48只,随机分为假手术组(S组)、体外循环组(C组)、U50488H+体外循环组(K组)及U50488H+特异性U50488H拮抗剂(Nor-BNI)+体外循环组(NK组),每组各12只。4组大鼠于麻醉置管/体外循环后1 d行水迷宫检测。酶联免疫吸附法检测血清中白细胞介素-6、中枢神经特异蛋白、肿瘤坏死因子α的浓度;免疫蛋白印记检测海马caspase-3表达的变化。结果 C组、K组、NK组的海马神经元凋亡阳性细胞积分吸光度值、caspase-3蛋白表达及血清白细胞介素-6、中枢神经特异蛋白、肿瘤坏死因子α浓度均高于S组; C组、NK组的海马神经元凋亡阳性细胞积分吸光度值、caspase-3蛋白表达及血清白细胞介素-6、中枢神经特异蛋白、肿瘤坏死因子α浓度均高于K组,组间比较,差异均有统计学意义(P <0. 05)。与S组比较,C组、K组、NK组大鼠逃避潜伏期时间明显延长,空间探索试验进入目标象限的次数明显减少;与C组比较,K组大鼠平均逃避潜伏期时间明显缩短,空间探索试验中进入目标象限的次数明显增多,差异有统计学意义(P <0. 05)。结论 U50488H可在一定程度降低体外循环诱发的大鼠海马细胞凋亡及炎症反应,对体外循环后认知功能有一定保护作用。

Objective To investigate the effect of U50488H on cognitive function and hippocampal cell apoptosis by CPB in rats.Methods Forty-eight healthy adult male SD rats of clean grade were randomly divided into sham operation group(Group S),cardiopulmonary bypass group(Group C),U50488H+CPB group(Group K),U50488H+specific U50488H antagonist+CPB group(Group NK),with 12 rats in each group.The rats in the 4 groups were tested for water maze 1 day after anesthesia catheterization/extracorporeal circulation.Apoptotic morphology of hippocampal tissue was observed by HE staining,IL-6,S100βand TNF-αin serum were detected by ELISA.The expression changes of caspase-3 protein was detected by westen-blot.Results The values of integral-absorbance,expression of caspase-3 protein,IL-6,S100βand TNF-αin hippocampal neurons of Group C,Group K and Group NK were higher than those of Group S.The hippocampal neuron apoptosis positive cell integral absorbance value,caspase-3 protein expression,IL-6,S100βand TNF-αconcentration in group C and NK were all higher than those in Group K(P<0.05).Compared with Group S,the escape latency time of rats in Group C,Group K and Group NK was significantly prolonged,and the number of space exploration experiments entering the target quadrant was significantly reduced.Compared with Group C,the average escape latency time of rats in Group K was significantly shortened,and the number of entering the target quadrant was significantly increased in the space exploration experiment(P<0.05).Conclusion U50488H could reduce hippocampal cell apoptosis by cardiopulmonary bypass in rats to some extent,and protect the cognitive function in rates.