神经炎症介导海马γ振荡异常在术后认知功能障碍中的作用

The role of neuroinflammation-mediated hippocampal oscillation abnormalities in postoperative cognitive dysfunction

目的术后认知功能障碍(POCD)是手术麻醉后一种常见的中枢神经系统并发症,文章探讨神经炎症介导海马γ振荡异常在POCD中的作用。方法 48只18~20月龄雄性C57BL/6小鼠,随机数字表法分为3组(n=16):对照组、手术组及手术+米诺环素组。采用七氟醚麻醉+剖腹探查术建立POCD动物模型,每组中随机选择11只于术后第4、5、6天行旷场、新物体识别和条件恐惧实验,术后第7天取小鼠海马组织检测海马炎症因子表达变化,CA1场电位检测。结果手术组小鼠新物体探索时间[(21.5±2.5)s]、辨别指数[(49.0±2.9)%]与场景关联僵直时间[(45±7)s]均较对照组[(33.5±2.7)s、(63.1±5.2)%、(79±8)s]显著降低(P<0.05)。与手术组比较,手术+米诺环素组新物体探索时间[(36.1±2.8)s]、辨别指数[(61.1±4.5)%]与场景关联僵直时间[(61.1±4.5)s]均显著增加(P<0.05)。手术组小鼠海马IL-1β[(9.19±1.10)pg/mg]与IL-6[(6.10±0.88) pg/mg]水平较对照组[(4.64±0.43)、(3.42±0.32)pg/mg]显著增高(P<0.05)。与手术组比较,手术+米诺环素组IL-1β[(5.90±0.67)pg/mg]与IL-6[(4.35±0.57) pg/mg]水平显著降低(P<0.05)。在新事物识别实验中:与对照组比较,手术组小鼠海马CA1区γ振荡均显著降低(P<0.05)。与手术组比较,手术+米诺环素组海马CA1区γ振荡显著增加(P<0.05)。在场景关联环境中:与对照组比较,手术组小鼠海马CA1区γ振荡显著降低(P<0.05)。与手术组比较,手术+米诺环素组海马CA1区γ振荡显著增加(P<0.05)。结论神经炎症介导海马γ振荡异常很可能在POCD中发挥关键作用。

Objective Postoperative cognitive dysfunction(POCD) is a common complication of central nervous system(CNS) after surgical anaesthesia. This paper investigates the role of neuroinflammation-mediated hippocampal oscillation abnormalities in POCD. Methods Forty-eight elderly(18-20 months old) male C57 BL/6 mice were randomly divided into three groups(n=16): control group, surgery group and surgery+minocycline group. An animal model of POCD was established by sevoflurane anesthesia plus exploratory laparotomy. Eleven mice in each group were randomly selected to perform open-field, novel object recognition test and fear conditioning test on the 4 th, 5 th and 6 th postoperative days. Hippocampal tissues of mice were taken on the 7 th day to detect changes in the expression of inflammatory factors in the hippocampus and CA1 local field potential(LFP). Results The time of novel object recognition[(21.5±2.5)s], the recognition ratio [(49.0±2.9)%] and the freezing time to context[(45±7)s] in the surgery group significantly decreased(P<0.05) than those in the control group [(33.5±2.7)s,(63.1±5.2)%, and(79±8)s].Compared with the surgery group, the time of novel object recognition [(36.1±2.8)s], the recognition ratio [(61.1±4.5)%] and the freezing time to context [(61.1±4.5)s] in the surgery+minocycline group significantly increased(P<0.05). The levels of hippocampal IL 1β[(9.19±1.10) pg/mg] and IL 6 [(6.10±0.88) pg/mg] in the surgery group were significantly higher than those in the control group(4.64±0.43 and 3.42±0.32) pg/mg)(P<0.05). Compared with the surgery group, the IL1β[(5.90±0.67) pg/mg] and IL6 [(4.35±0.57) pg/mg] levels in the surgery+minocycline group significantly decreased(P<0.05). In the novel object recognition experiment, compared with the control group, the gamma oscillation in the hippocampal CA1 area of the surgery group significantly decreased(P<0.05). In the scene of correlation, compared with the control group, the oscillations in the hippocampal CA1 region of the surgery group significantly reduced(P<0.05). Compared with the surgery group, the oscillation in the CA1 area of the hippocampus significantly increased in the operation+minocycline group(P<0.05). ConclusionNeuroinflammation-mediated hippocampal oscillation abnormalitiesmight play a key role inPOCD.