SIRT2对脓毒症小鼠远期抑郁的影响及其机制研究

发布时间：2018-01-25 19:16

本文关键词： 沉默信息调节基因核因子-κB 抑郁脓毒症　出处：《华中科技大学学报(医学版)》2017年04期 　论文类型：期刊论文

【摘要】：目的探讨沉默信息调节基因2(SIRT2)对脓毒症小鼠远期抑郁的影响及其机制。方法腹腔注射内毒素(LPS)制备脓毒症小鼠模型,实验动物随机分成3组:对照组(Control)、脓毒症组(LPS)、干预组(AGK2+LPS)。通过悬尾实验、强迫游泳实验和糖水偏好实验来评估小鼠抑郁状况,Western blot法检测小鼠脑内海马组织SIRT2和乙酰化核因子-κB(NF-κB)蛋白表达,免疫荧光法检测小鼠脑内海马组织Iba1活性,ELISA法测定海马组织肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)水平。结果脓毒症小鼠远期出现明显的抑郁相关表现,脑组织SIRT2蛋白表达水平降低,乙酰化NF-κB p65蛋白表达明显增加,小胶质细胞活化增加,脑组织内TNF-α和IL-1β水平增加(P0.05,P0.01)。SIRT2特异性抑制剂AGK2抑制脑组织内SIRT2的表达(P0.01),而且乙酰化NF-κB p65蛋白表达、小胶质细胞活化和脑组织内TNF-α和IL-1β水平均进一步增加(P0.05,P0.01),远期抑郁相关表现也明显加重(P0.01)。结论在脓毒症小鼠中,SIRT2表达下降抑制NF-κB去乙酰化,进而加重大脑组织炎症反应和远期抑郁。
[Abstract]:Objective to investigate the effect and mechanism of silencing signal regulating gene (2SIRT2) on long-term depression in septic mice. Methods mice model of sepsis was induced by intraperitoneal injection of endotoxin (LPS). Experimental animals were randomly divided into three groups: control group (control group), sepsis group (LPSN) and intervention group (AGK2 LPSN). Forced swimming test and sugar water preference test were used to evaluate depression in mice. Western blot method was used to detect the expression of SIRT2 and acetylated nuclear factor- 魏 B (NF- 魏 B) protein in hippocampus of mice. The activity of Iba1 in hippocampus of mice was detected by immunofluorescence method. The levels of tumor necrosis factor- 伪 (TNF- 伪) and interleukin-1 尾 (IL-1 尾) in hippocampus were measured by ELISA method. The expression of SIRT2 protein decreased, the expression of acetylated NF- 魏 B p65 protein increased, and the activation of microglia increased. The levels of TNF- 伪 and IL-1 尾 in brain tissue increased P0.05P0.01P0.01N. SIRT2 specific inhibitor AGK2 inhibited the expression of SIRT2 in brain tissue (P0.01). Furthermore, the expression of acetylated NF- 魏 B p65, the activation of microglia and the levels of TNF- 伪 and IL-1 尾 in brain tissue were further increased. Conclusion in sepsis mice, the decreased expression of SIRT2 inhibits the deacetylation of NF- 魏 B and exacerbates the inflammatory response of brain tissue and long-term depression.
【作者单位】：华中科技大学同济医学院附属同济医院急诊内科;华中科技大学同济医学院基础医学院药理学系;
【基金】：湖北省自然科学基金资助项目(No.2015CFB284)
【分类号】：R459.7;R749.4
【正文快照】： 脓毒症是重症监护病房(ICU)患者死亡的主要原因,占10%到50%[1]。脓毒症相关性脑病(septicassociated encephalopathy,SAE)是由脓毒症引起的中枢神经系统弥散性功能障碍,是ICU常见的临床综合征,发病率高达70%,主要表现为精神状态和认知功能的改变。脓毒症患者一旦合并SAE,其病

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