NF-κB在脓毒症老龄小鼠认知功能减退中的作用  

Role of nuclear factor kappa B in cognitive decline in aged mice with sepsis

作　　者：陈伟明[1] 温博伦 陈晓彤[2] 詹鸿[1] 王寿平[1] 周立兵 Chen Weiming1, Wen Bolun1, Chen Xiaotong2, Zhan Hong1, Wang Shouping1, Zhou Libing3(1. Department of Anesthesiology, Third Affiliated Hospital of Guangzhou Medical University, Gwangzhou 510150, China ; 2.Boji Medical Care Center, SUN Yat-Sen Memorial Hospital, SUN Yat-Sen University, Guangzhou 510120, China ; 3.Guangdong- HongKong-Macao Institute of CNS Regeneration, Guangzhou 510632, China)

机构地区：[1]广州医科大学附属第三医院麻醉科,510150 [2]中山大学孙逸仙纪念医院博济医疗中心,广州市510120 [3]暨南大学粤港澳中枢神经再生研究院, 广州市510632

出　　处：《中华麻醉学杂志》2018年第4期477-480,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81271223）;广东省自然科学基金（S2012010009065、2014A030313112）

摘　　要：目的 评价NF-κB在脓毒症老龄小鼠认知功能减退中的作用.方法 SPF级健康老年雌性C57BL/6小鼠45只,10～12月龄,体重20～ 30 g,采用随机数字表法分为3组（n=15）：对照组（C组）、脓毒症组（Sep组）和NF-κB特异性抑制剂PDTC组（PDTC组）.Sep组和PDTC组腹腔注射LPS 250 μg/kg,1次/d,连续7 d;PDTC组于LPS注射前30 min腹腔注射PDTC 50 mg/kg,1次/d,连续7d.末次给药2h时每组随机取5只小鼠心脏穿刺取血,随后处死取海马,采用ELISA法测定血浆和海马TNF-α、IL-1β、IL-6的水平.其余于末次给药24h时行旷场实验、高架十字实验和Morris水迷宫实验.结果 与C组比较,Sep组血浆和海马TNF-α、IL-1β、IL-6的水平升高,中央区活动时间缩短,开臂时间百分比降低,进入开臂和闭臂次数减少,逃避潜伏期延长,原平台所在象限停留时间缩短,穿越平台次数减少（P＜0.05）;与Sep组比较,PDTC组血浆和海马TNF-α、IL-1β、IL-6的水平降低,中央区活动时间延长,开臂时间百分比升高,进入开臂和闭臂次数增加,逃避潜伏期缩短,原平台所在象限停留时间延长（P＜0.05）.结论 NF-κB参与了脓毒症老龄小鼠认知功能减退的过程.Objective To evaluate the role of nuclear factor kappa B （NF-κB） in cognitive decline in aged mice with sepsis.Methods Forty-five SPF healthy aged female C57BL/6 mice,aged 10-12 months,weighing 20-30 g,were assigned into 3 groups （n=15 each） using a random number table：control group （group C）,sepsis group （group Sep） and NF-κB selective inhibitor pyrrolidine dithiocarbamate （PDTC） group （group PDTC）.Lipopolysaccharide 250 μg/kg was injected intraperitoneally once a day for 7 consecutive days in Sep and PDTC groups,and in addition PDTC 50 mg/kg was injected intraperitoneally at 30 min before lipopolysaccharide injection once a day for 7 consecutive days in group PDTC.The equal volume of normal saline was given in group C.Five mice in each group were sacrificed at 2 h after the last administration,cardiac puncture was performed and blood samples were collected,and then the mice were sacrificed and hippocampi were harvested for determination of the levels of tumor necrosis factor-α （TNF-α）,interleukin-1β （IL-1β） and IL-6 in plasma and hippocampal tissues using enzyme-linked immunosorbent assay.Cognitive function was assessed using open field,elevated plus maze and Morris water maze tests at 24 h after the last administration in the other mice left in each group.Results Compared with group C,the levels of TNF-α,IL-1β and IL-6 in plasma and hippocampal tissues were significantly increased,the time of movement at the central region was shortened,the percentage of time spent in the open arms and number of entries into the open and closed arms were decreased,the escape latency was prolonged,the time of staying at the original platform quadrant was shortened,and the frequency of crossing the platform was decreased in group Sep （P〈0.05）.Compared with group Sep,the levels of TNF-α,IL-1β5 and IL-6 in plasma and hippocampal tissues were significantly decreased,the time of movement at the central region was prolonged,the percentage of time spent in the open arms and number of

关 键 词：NF-ΚB 脓毒症 认知障碍 老年人 

分 类 号：R459.7[医药卫生—急诊医学]