尼克酰胺腺嘌呤二核苷酸联合目标体温管理对重型颅脑创伤大鼠的神经保护作用  

Neuroprotective effect of nicotinamide adenine dinucleotide combined with targeted temperature management on rats with severe traumatic brain injury

作　　者：时华 涂悦 王振国 吴焕成 刘洋[4] SHI Hua;TU Yue;WANG Zhen-guo;WU Huan-cheng;LIU Yang(The First Department of Neurosurgery,Characteristic Medical Center of Chinese People′s Armed Police Forces,Tianjin 300162,China;Brain Center,Characteristic Medical Center of Chinese People′s Armed Police Forces,Tianjin 300162,China;Graduate School,Tianjin Medical University,Tianjin 300070,China;Department of Neurology,the Fourth People′s Hospital of Shanghai,Shanghai 200081,China)

机构地区：[1]武警特色医学中心神经外一科,天津市300162 [2]武警特色医学中心脑科中心,天津市300162 [3]天津医科大学研究生院,天津市300070 [4]上海市第四人民医院神经内科,上海市200081

出　　处：《广西医学》2019年第16期2084-2087,2093,共5页Guangxi Medical Journal

基　　金：国家自然科学基金(31200809);天津市科技计划(16ZXHLSY00120);天津市北辰区科技计划项目(2018-SHGY-09);上海市虹口区卫计委项目(虹卫1802-06)

摘　　要：目的 探讨尼克酰胺腺嘌呤二核苷酸(NAD)联合目标体温管理(TTM)对重型颅脑创伤(STBI)大鼠的神经保护作用。方法 将60只雄性SD大鼠随机分为STBI组、STBI+TTM组(S+T组)、STBI+NAD组(S+N组)、STBI+TTM+NAD组(S+T+N组)和对照组,每组12只。对照组不做任何处理,对其他组大鼠使用脑皮质撞击仪构建重型STBI模型。S+T组和S+T+N组在建模后10min行TTM治疗。于造模后第2天起,S+N组和S+T+N组大鼠给予腹腔注射烟酰胺单核苷酸,STBI组及S+T组大鼠给予注射等量生理盐水。7d后,对各组大鼠进行改良神经功能损伤量表(mNSS)评分。处死大鼠后获取脑组织,采用干湿比重法测定脑水肿程度,检测NAD、丙二醛、肿瘤坏死因子α(TNF-α)、S100β蛋白、水通道蛋白4(AQP4)和紧密桥接蛋白(TJP)表达水平。结果 与对照组比较,STBI组大鼠脑含水量增加,mNSS评分下降,且脑组织丙二醛、TNF-α、S100β蛋白、AQP4和TJP的表达水平均升高(均P<0.05)。与STBI组比较,S+T组、S+N组、S+T+N组的mNSS评分、脑组织S100β蛋白和AQP4表达水平均降低,且S+T+N组脑组织含水量减少,脑组织丙二醛、TNF-α、TJP水平降低(P<0.05)。与S+T组、S+N组比较,S+T+N组mNSS评分以及脑组织TNF-α、S100β蛋白、TJP水平均降低(均P<0.05)。结论 联合应用NAD与TTM可发挥协同作用,更好地降低STBI后炎症及氧化应激水平,减轻脑水肿,从而发挥神经保护作用。Objective To investigate the neuroprotective effect of nicotinamide adenine dinucleotide(NAD) combined with targeted temperature management(TTM) on rats with severe traumatic brain injury(STBI).Methods Sixty male SD rats were randomly divided into STBI group,STBI+TTM group(S+T group),STBI+NAD group(S+N),STBI+TTM+NAD group(S+T+N group) and control group,with 12 rats in each group.No treatment was performed in the control group,while STBI model was constructed using a cortical perforator in the rats of the other groups.Ten minutes after modeling,TTM therapy was conducted in the S+T and S+T+N groups.From the second day after modeling,intraperitoneal injection of nicotinamide mononucleotide was performed in the rats of the S+N and S+T+N groups,and injection of normal saline with equal volume in the rats of the STBI and S+T groups.Seven days later,the rats in each group were assessed using the Modified Neurological Severity Scale(mNSS) score.Then brain tissues were obtained after rats were killed,degree of encephaledema was determined using dry/wet weighting method,and the expression levels of NAD,malondialdehyde,tumor necrosis factor α(TNF-α),S100β protein,aquaporin 4(AQP4) and tight junction protein(TJP) were detected.Results Compared to the control group,rats in the STBI group had increased moisture content of brain tissue and decreased mNSS score,along with higher expression levels of brain tissue malondialdehyde,TNF-α,S100β protein,AQP4 and TJP(all P<0.05).Compared to the STBI group,the S+T,S+N,and S+T+N groups exhibited lower mNSS score and lower expression levels of brain tissue S100β protein and AQP4,moreover,the S+T+N group achieved less moisture content of brain tissue,and lower levels of brain tissue malondialdehyde,TNF-α and TJP(all P<0.05).The S+T+N group got lower mNSS score as well as lower levels of brain tissue TNF-α,S100β protein and TJP as compared with the S+T and S+N groups(all P<0.05).Conclusion The combined application of NAD and TTM can exert a synergistic effect,can better reduce infl

关 键 词：颅脑创伤 重型 尼克酰胺腺嘌呤二核苷酸 目标体温管理 神经保护 大鼠 

分 类 号：R651.15[医药卫生—外科学]