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

作　　者：孙凡[1] 鲍红光[1] 斯妍娜[1] 徐亚杰[1] 潘笑笑 曾令清[1] 景灵 

机构地区：[1]南京医科大学附属南京医院南京市第一医院麻醉科,210006

出　　处：《临床麻醉学杂志》2017年第4期382-385,共4页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金(81401620);江苏省临床医学科技专项(BL2014012)

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30min和4h分别腹腔注射生理盐水5ml/kg,B组大鼠于CLP术后30 min和4h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。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 5ml/kg 30 min and 4hafter CLP,respectively.The rats in group B were intraperitoneally injected with sodium butyrate 500mg/kg 0.5hand 4hafter CLP,respectively.All animals were performed Morris water maze test on4 th 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.

关 键 词：脓毒症相关性脑病 认知功能 正丁酸钠 HMGB1乙酰化 

分 类 号：R459.7[医药卫生—急诊医学] R747.9[医药卫生—治疗学]