SIRT1在内毒素性脑损伤小鼠线粒体功能障碍中的作用  

Role of SIRT1 in mitochondrial dysfunction in mice with lipopolysaccharide-induced brain injury

作　　者：穆蕊 李翠[1] 宫丽荣[1] 余剑波[1] Mu Rui;Li Cui;Gong Lirong;Yu Jianbo(Department of Anesthesiology and Critical Care Medicine,Nankai Clinical College of Tianjin Medical University(Tianjin Nankai Hospital),Tianjin 300100,China)

机构地区：[1]天津医科大学南开临床学院(天津市南开医院)麻醉科与重症医学科,天津300100

出　　处：《中华麻醉学杂志》2023年第2期216-220,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金青年科学基金(81903941,82104584)。

摘　　要：目的评价海马沉默信息因子1(SIRT1)在内毒素性脑损伤小鼠线粒体功能障碍中的作用。方法清洁级雄性C57BL/6小鼠80只,6~8周龄,采用随机数字表法分为4组(n=20):对照组(C组)、内毒素性脑损伤组(LPS组)、内毒素性脑损伤+SIRT1抑制剂组(LPS+E组)和内毒素性脑损伤+SIRT1激动剂(LPS+S组)。静脉注射LPS 10 mg/kg制备小鼠内毒素性脑损伤模型。于注射LPS前72 h时,LPS+E组腹腔注射SIRT1抑制剂EX52710 mg/kg,其余3组腹腔注射等容量DMSO;于注射LPS前30 min时LPS+S组腹腔注射SIRT1激动剂SRT1720 100 mg/kg,其余3组腹腔注射等容量DMSO。注射LPS 24 h时行新物体识别实验,安乐处死小鼠,取海马组织行尼氏染色,光镜下观察病理学结果,并计数海马CA1区正常神经元;采用分光光度法测定海马ATP含量和线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅲ、Ⅳ的活性,Jc-1染色法检测线粒体膜电位(MMP),透射电镜观察神经元线粒体超微结构。结果与C组比较,LPS组、LPS+S组和LPS+E组新物体识别指数、海马正常神经元计数、线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅲ、Ⅳ的活性、MMP和ATP含量降低(P<0.05),海马神经元发生损伤,线粒体肿胀、嵴结构断裂。与LPS组比较,LPS+E组新物体识别指数、海马线粒体呼吸链复合物活性、MMP和ATP含量降低(P<0.05),海马神经元损伤进一步加重,线粒体肿胀及嵴结构断裂加剧;LPS+S组新物体识别指数、海马线粒体呼吸链复合物活性、MMP和ATP含量升高(P<0.05),海马神经元损伤减轻,线粒体肿胀及嵴结构断裂改善。结论SIRT1激活可改善线粒体功能障碍,减轻小鼠内毒素性脑损伤。Objective To evaluate the role of silent information regulator sirtuin 1(SIRT1)in mitochondrial dysfunction in mice with lipopolysaccharide(LPS)-induced brain injury.Methods Eighty clean-grade male C57BL/6 mice,aged 6-8 weeks,were divided into 4 groups(n=20 each)by the random number table method:control group(group C),LPS-induced brain injury group(LPS group),LPS-induced brain injury plus SIRT1 inhibitor EX527 group(LPS+E group),and LPS-induced brain injury plus SIRT1 agonist SRT1720 group(LPS+S group).Brain injury was induced by intravenous injection of LPS 10 mg/kg.EX52710 mg/kg was intraperitoneally injected at 72 h before LPS injection in group LPS+E,and the equal volume of dimethyl sulfoxide was intraperitoneally injected instead in the other three groups.SRT1720 100 mg/kg was intraperitoneally injected at 30 min before LPS injection in group LPS+S,and the equal volume of dimethyl sulfoxide was intraperitoneally injected instead in the other three groups.The novel object recognition test was performed at 24 h after LPS injection,then the mice were sacrificed,and hippocampal tissues were harvested for determination of the number of the normal neurons in the hippocampal CA1 area,ATP content and activities of mitochondrial respiratory chain complexesⅠ,Ⅱ,ⅢandⅣ(by spectrophotometry),and mitochondrial membrane potential(MMP)(by Jc-1 staining)and for microscopic examination of pathological changes(by Nissl staining)and ultrastructure of neuronal mitochondria(with a transmission electron microscope).Results Compared with group C,the preference index in novel object recognition,normal neuron count,activities of mitochondrial respiratory chain complexesⅠ,Ⅱ,ⅢandⅣ,MMP and ATP content were significantly decreased(P<0.05),damage to hippocampal neurons was found,mitochondrial swelling was observed and cristae structure ruptured in LPS,LPS+S and LPS+E groups.Compared with group LPS,the preference index in novel object recognition,activities of mitochondrial respiratory chain complexes,MMP and ATP content wer

关 键 词：内毒素血症 脑损伤 抗衰老酶1 线粒体 

分 类 号：R741[医药卫生—神经病学与精神病学]