摘要
目的评价沉默信息调节因子1(SIRT1)信号通路在右美托咪定(DEX)减轻老龄大鼠术后认知功能障碍(POCD)中的作用。方法取清洁健康的雄性SD大鼠72只,18~20月龄,体质量500~700 g,采用随机数字表法分为4组。正常对照组(Control组):未经处理的正常老龄大鼠;POCD组:手术处理建立的POCD模型大鼠;DEX组:术前DEX预处理的POCD模型大鼠;SIRT1抑制剂组(EX527组):术前DEX和EX527预处理的POCD模型大鼠,18只/组。DEX组和EX527组术前30 min腹腔注射右美托咪定25μg/kg,Control组和POCD组腹腔注射等量的生理盐水。30 min后POCD组、DEX组及EX527组行剖腹探查术,维持手术时间30 min。EX527组术前5 min静脉注射EX527 1μg/kg。Control组不做任何处理。分别于术后1 d(T_1)、3 d(T_2)和5 d(T_3)时每组随机选取6只大鼠进行Morris水迷宫实验,记录逃避潜伏期和穿越平台次数以测定认知功能,之后立即处死大鼠并取其海马,采用ELISA法测定各组大鼠海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量,Western blot法分别检测海马神经元SIRT1和NF-κB的表达。结果与Control组相比,POCD组和EX527组逃避潜伏期延长,穿越平台次数减少,TNF-α、IL-6含量升高,海马神经元SIRT1表达下调,NF-κB表达升高(P<0.05);与POCD组相比,DEX组逃避潜伏期缩短,穿越平台次数增加,TNF-α、IL-6含量降低,海马神经元SIRT1表达上调,NF-κB表达降低(P<0.05),EX527组与POCD组相比上述指标差异无统计学意义(P>0.05);与DEX组相比,EX527组逃避潜伏期延长,穿越平台次数减少,TNF-α、IL-6含量升高,海马神经元SIRT1表达下调,NF-κB表达升高(P<0.05)。结论右美托咪定减轻老龄大鼠术后认知功能障碍可能通过SIRT1信号通路发挥作用。
Objective To explore the role of silent information regulator 1（SIRT1） signaling pathway in mediating the effect of dexmedetomidine（DEX） to alleviate postoperative cognitive dysfunction（POCD） in aged rats. Methods Seventy-two healthy male Sprague-Dawley rats aged 18-20 months（weighing 500-700 g） were randomized equally into normal control group,POCD model group, DEX pretreatment group, and DEX and SIRT1 inhibitor（EX527） pretreatment group. In the latter 2 groups, DEX（25 μg/kg） was injected intraperitoneally in the rats 30 min before the operation, and normal saline was injected instead in the other 2 groups; in EX527 group, EX527（1 μg/kg） was injected intravenously 5 min before the operation. In all but the control group, the rats were subjected to laparotomy lasting 30 min, and on days 1, 3, and 5 following the operation, 6 rats were randomly selected from each group for Morris water maze test to evaluate their cognitive functions. Immediately after the test, the rats were sacrificed and the hippocampus was collected for determination of the levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） using ELISA; Western blotting was used to detect the expression of SIRT1 and nuclear factor-κB（NF-κB） in the hippocampal neurons. Results Compared with the control rats, the rats in POCD group and EX527 group showed significantly prolonged escape latency, decreased frequency of crossing the original platform, increased TNF-α and IL-6 levels, lowered SIRT1 expression in the hippocampal neurons, and increased NF-κB expression（P0.05）, and these parameters were comparable between POCD group and EX527 group（P0.05）. DEX pretreatment significantly alleviated cognitive dysfunction and attenuated the changes in TNF-α, IL-6, SIRT1, and NF-κB expressions induced by the operation（P0.05）, and EX527 pretreatment of the rats obviously blocked the effects of DEX（P0.05）. Conclusion DEX alleviates POCD in aged rats probably via SIRT1 signaling pathway.
作者
方四通
陈勇
姚鹏
李依玲
杨玉军
徐国海
FANG Sitong;CHEN Yong;YAO Peng;LI Yiling;YANG Yujun;XU Guohai(Department of Anesthesiology,Second Affiliated Hospital of Nanchang Universit;Key Laboratory of Anesthesiology of Jiangxi Province,Nanchang 330006,China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2018年第9期1071-1075,共5页
Journal of Southern Medical University
基金
国家自然科学基金(81560193
8176050165)
江西省卫计委中医药科技计划项目(2016B094)
江西省卫计委科技计划项目(20175205)
南昌大学第二附属医院科技计划青年基金(2016YNQN12008)~~
