[1]方四通,陈勇,姚鹏,等.右美托咪定可能通过SIRT1信号通路减轻老龄大鼠的术后认知功能障碍[J].南方医科大学学报,2018,(09):1071.[doi:10.12122/j.issn.1673-4254.2018.09.08]
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右美托咪定可能通过SIRT1信号通路减轻老龄大鼠的术后认知功能障碍()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年09期
页码:
1071
栏目:
出版日期:
2018-09-30

文章信息/Info

Title:
Dexmedetomidine alleviates postoperative cognitive dysfunction in aged rats probably via silent information regulator 1 pathway
作者:
方四通陈勇姚鹏李依玲杨玉军徐国海
关键词:
沉默信息调节因子1右美托咪定老年认知障碍
Keywords:
sirtuin 1 dexmedetomidine aged cognition disorders
DOI:
10.12122/j.issn.1673-4254.2018.09.08
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25 μg/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 1 μg/kg。Control组不做任何处理。分别于术后1 d(T1)、3 d(T2)和5 d(T3) 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。
Abstract:
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 (P<0.05), and these parameters were comparable between POCD group and EX527 group (P>0.05). DEX pretreatment significantly alleviated cognitive dysfunction and attenuated the changes in TNF-α, IL-6, SIRT1, and NF-κB expressions induced by the operation (P<0.05), and EX527 pretreatment of the rats obviously blocked the effects of DEX (P<0.05). Conclusion DEX alleviates POCD in aged rats probably via SIRT1 signaling pathway.

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更新日期/Last Update: 1900-01-01