文章摘要
HMGB1乙酰化在脓毒症相关性脑病中的作用
Effects of acetylated HMGB1 in rats with sepsis associated encephalopathy
  
DOI:
中文关键词: 脓毒症相关性脑病  认知功能  正丁酸钠  HMGB1乙酰化
英文关键词: Sepsis associated encephalopathy  Cognitive function  Sodium butyrate  Acetylated HMGB1
基金项目:国家自然科学基金(81401620),江苏省临床医学科技专项(BL2014012)
作者单位
孙凡 210006,南京医科大学附属南京医院,南京市第一医院麻醉科 
鲍红光  
斯妍娜  
徐亚杰  
潘笑笑  
曾令清  
景灵  
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中文摘要:
      目的 探讨高迁移率族蛋白1(HMGB1)乙酰化在脓毒症相关性脑病(SAE)大鼠认知功能中的作用及HMGB1抑制剂对其的影响。方法 成年雄性SD大鼠48只,随机分为三组,每组16只:假手术组(S组)、盲肠结扎穿孔术组(C组)、盲肠结扎术+正丁酸钠组(B组)。采用盲肠结扎穿孔法(CLP)建立SAE模型,S组只做假手术。S组和C组大鼠于CLP术后30 min和4 h分别腹腔注射生理盐水5 ml/kg,B组大鼠于CLP 术后30 min和4 h分别侧脑室注射正丁酸钠500 mg/kg。CLP术后第4天行Morris水迷宫测试,CLP术后第7天行空间探索实验,并记录探索时间。行为学测试结束后取大鼠海马组织,Western blot法测定IL-6浓度、脑源性神经营养因子(BDNF)、HMGB1和乙酰化HMGB1的含量。结果 C组逃避潜伏期明显长于S组,探索时间明显短于S组(P<0.05);B组逃避潜伏期明显短于C组,探索时间明显长于C组(P<0.05)。C组海马IL-6浓度、HMGB1和乙酰化HMGB1含量明显高于S组(P<0.05),BDNF含量明显低于S组(P<0.05);B组海马IL-6浓度、HMGB1和乙酰化HMGB1含量明显低于,BDNF含量明显高于C组(P<0.05)。结论 HMGB1抑制剂正丁酸钠可抑制SAE大鼠海马内HMGB1乙酰化的表达,减轻脓毒症诱发的认知功能损伤。
英文摘要:
      Objective To investigate the effects of acetylated HMGB1 on cognitive function in rats with sepsis associated encephalopathy (SAE) and the effect of HMGB1 inhibitor. Methods Forty-eight males mice were randomly assigned to three groups (n=16): sham group (group S), cecal ligation puncture group (group C), cecal ligation puncture+sodium butyrate group (group B). Cecal ligation puncture was applied to establish the SAE model, and group S received sham operation. Rats in groups S and C were injected with normal saline 5 ml/kg 30 min and 4 h after CLP, respectively. The rats in group B were intraperitoneally injected with sodium butyrate 500 mg/kg 0.5 h and 4 h after CLP, respectively. All animals were performed Morris water maze test on 4th day after operation, and the exploring time of space exploration experiments were assessed on 7th day after CLP surgery. IL-6, BDNF, HMGB1 and acetylated HMGB1 expression in hippocampus of all rats were determined by Western Blot. Results Compared with group S, the latency of rats in group C was longer and the exploring time was shorter (P<0.05). Compared with group C, the latency of rats in group B was shorter and the exploring time was longer (P<0.05). Compared with group S, the expression of IL-6, HMGB1 and acetylated HMGB1 in group C increased (P<0.05) and the level of BDNF decreased (P<0.05). Compared with group C, the expression of IL-6, HMGB1 and acetylated HMGB1 in group B decreased (P<0.05) and the level of BDNF increased (P<0.05). Conclusion HMGB1 inhibitor sodium butyrate can inhibit the expression of acetylated HMGB1 in the hippocampus of SAE rats, and reduce the cognitive impairment induced by sepsis.
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