目的 探讨环腺苷酸应答元件结合蛋白(CREB)与脑源性神经营养因子(BDNF)通路在老年小鼠术后认知功能障碍发病机制中的作用.方法 72只老年C57BL/6小鼠随机分为4组:对照组、异氟醚组、手术组和异氟醚+手术组,每组18只,分别施以假手术、1.8％异氟醚吸入1.5h、局麻腹部手术和1.8％异氟醚吸入1.5h+局麻腹部手术.术后行条件恐惧行为学实验评估各组小鼠认知功能,并分别于术后第1、3、7天行Western blot实验检测各组小鼠海马组织CREB、Ser133位点磷酸化CREB(p-CREB)以及BDNF的表达情况.结果 与其他3组比较,手术组小鼠术后第3天场景测试和声音测试凝滞时间百分比降低,术后第1、7天场景测试凝滞时间百分比降低,且小鼠术后第1、3天海马p CREB/CREB比值降低,术后第3、7天BDNF表达减少(P＜0.05,P＜0.01).结论 腹部手术可致老年小鼠术后早期认知功能损害,异氟醚吸入全麻下行腹部手术有一定认知保护作用,CREB/BDNF通路受到抑制是老年小鼠术后认知功能障碍发病机制之一.%Objective To study the role of cyclic AMP response element binding protein (CREB)/ brain derived neurotrophic factor (BDNF) pathway in pathogenesis of POCD in aged mice.Methods Seventy-two aged male C57BL/6 mice were randomly divided into control group,isoflurane group,operation group,and isoflurane +operation group (18 in each group).After they received sham operation,1.8％ isoflurane inhalation for 1.5 h,abdominal operation under local anesthesia and abdominal operation under local anesthesia+1.8％ isoflurane inhalation for 1.5 h respectively,their cognitive function was assessed by fear conditioning behavioral test.Expressions of CREB,BDNF and p-CREB in hippocampus were detected by Western blot on days 1,3,7 after operation.Results Context and tone test showed the percentage of freezing time was lower in operation group than in other 3 groups on day 3 after operation.Context test showed the percentage of freezing time was lower in operation group than in other 3 groups on days 1 and 7 after operation.The ratio of p-CREB/CREB in hippocampus was lower in operation group than in other 3 groups on days 1 and 3 after operation.The expression level of BDNF was lower in operation group than in other 3 groups on days 3 and 7 after operation (P＜0.05,P＜0.01).Conclusion Abdominal operation can induce early postoperative cognitive impairment in aged mice while abdominal operation under isoflurane inhalation anesthesia can protect the cognitive function in aged mice.Inhibition of CREB/BDNF pathway is the mechanisms for POCD in aged mice.
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