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目的 探讨U50488H对CPB诱发大鼠术后认知功能障碍的影响.方法 清洁级成年雄性SD大鼠48只,体重400～ 450 g,采用随机数字表法分为3组(n=16):假手术组(S组)、CPB组和CPB+U50488H组(U组).CPB组行CPB 60 min;U组于CPB前30 min时左侧脑室注射U50488H1.5 mg/kg,然后行CPB 60 min.于CPB后1d时,每组取8只大鼠,采集静脉血标本,采用ELISA法检测血清S100β蛋白、IL-1β和TNF-α的浓度,然后处死大鼠,取右侧海马组织,HE染色后光镜下观察病理学结果.于CPB后7d时,每组取8只大鼠,测定认知功能.结果 与S组比较,CPB组和U组血清S100β蛋白、IL-1β和TNF-α的浓度升高,逃避潜伏期延长,穿越原平台次数减少,目标象限游泳距离和停留时间缩短(P＜0.05);与CPB组比较,U组血清S100β蛋白、IL-1β和TNF-α的浓度降低,逃避潜伏期缩短,穿越原平台次数增加,目标象限的游泳距离和停留时间延长(P＜0.05),海马组织病理学损伤减轻.结论 U50488H可减轻CPB诱发大鼠术后认知功能障碍.

Objective To investigate the effect of U50488H on postoperative cognitive dysfunction induced by cardiopulmonary bypass (CPB) in rats.Methods Forty-eight adult male Sprague-Dawley rats,weighing 400-450 g,were divided into 3 groups (n=16 each) using a random number table:sham operation group (group S),CPB group and CPB plus U50488H group (group U).CPB was performed for 60 min in group CPB.U50488H 1.5 mg/kg was injected into the left lateral cerebral ventricle at 30 min prior to CPB,and then CPB was performed for 60 min in group U.Eight rats in each group were selected at 1 day after CPB,and venous blood samples were collected for determination of serum S100β protein,interleukin-lbeta (IL-1 β) and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay).Then the rats were sacrificed and right hippocampi were removed for examination of the pathological changes after haematoxylin and eosin staining.Eight rats were selected from each group at 7 days after CPB for assessment of cognitive function.Results Compared with group S,the concentrations of serum S100β protein,IL-1β and TNF-α were significantly increased in group CPB,and the escape latency was prolonged,the number of crossing original platform was reduced,and the swimming distance in target quadrant and time of staying at target quadrant were shortened in CPB and U groups (P＜0.05).Cormpared with group CPB,the concentrations of serum S100β protein,IL-1β and TNF-α were significantly decreased,the escape latency was shortened,the number of crossing original platform was increased,the swimming distance in target quadrant and time of staying at target quadrant were prolonged (P＜0.05),and the pathological changes of hippocampal tissues were significantly attenuated in group U.Conclusion U50488H can mitigate the postoperative cognitive dysfunction induced by CPB in rats.