烟酰胺核糖对酒精暴露小鼠抑郁样行为及肠黏膜通透性改善效果  

Alleviating Effect of Nicotinamide Ribose on Depressed-Like Behavior and Intestinal Mucosal Permeability in Alcohol-Exposed Mice

作　　者：姜雨杉 刘颖[2] 王子龙 薛美兰[2] 常志尚[3] 梁惠[1] JIANG Yushan;LIU Ying;WANG Zilong;XUE Meilan;CHANG Zhishang;LIANG Hui(School of Public Health,Qingdao University,Qingdao 266021,China;School of Basic Medicine,Qingdao University,Qingdao 266071,China;Public Support Platform for Biomedicine,Qingdao University,Qingdao 266021,China)

机构地区：[1]青岛大学公共卫生学院,山东青岛266021 [2]青岛大学基础医学院,山东青岛266071 [3]青岛大学生物医学公共支撑平台,山东青岛266021

出　　处：《食品科学》2020年第13期112-119,共8页Food Science

基　　金：国家自然科学基金面上项目(81573137;81872605);山东省重点研发项目(2017GSF18167)。

摘　　要：目的:探讨烟酰胺核糖(nicotinamide riboside,NR)作为一种营养补充剂对酒精暴露小鼠抑郁样行为及肠黏膜通透性的改善效果。方法:30只雄性C57BL/6J小鼠随机分为3组(10只/组),对照组和模型组每天给予0.2 mL生理盐水灌胃,NR干预组(NR组)每天给予400 mg/kg mb NR灌胃。每周一至周四上午8时至下午16时给予模型组和NR组小鼠新鲜配制的体积分数15%乙醇水溶液自由饮用,下午16时至次日上午8时给予其自来水自由饮用;对照组小鼠全天给予自来水自由饮用,周五、六切断3组小鼠一切水源,周日给予3组小鼠自来水自由饮用。干预期间3组小鼠自由进食,实验持续10周。采用旷场实验、糖水偏好实验和强迫游泳实验评价小鼠抑郁样行为;苏木精-伊红染色观察小鼠海马组织CA1区病理学改变;酶联免疫吸附实验检测各组小鼠血清中脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)及脂多糖(lipopolysaccharide,LPS)质量浓度;采用透射电子显微镜对小鼠空肠和结肠组织细胞连接装置超微结构进行观察;采用示踪实验观察小鼠空肠和结肠组织渗透性;免疫印迹实验检测小鼠空肠和结肠组织中紧密连接蛋白occludin及ZO-1表达水平。结果:与对照组和NR组相比,模型组小鼠在旷场实验的总运动距离和中央区域停留时间缩短,糖水偏爱度明显下降,同时,强迫游泳实验中模型组不动时间达到(168.6±34.4)s,较对照组((107.9±47.4)s)显著延长(P<0.05);NR干预后,其抑郁样行为较模型组明显改善。模型组小鼠海马CA1区出现部分神经细胞损伤,血清BDNF水平达到(438.9±46.7)pg/mL,较对照组((638.1±77.3)pg/mL)显著降低(P<0.05);NR干预后,神经细胞损伤得到一定程度修复,血清BDNF水平达到(735.7±55.7)pg/mL,较模型组显著升高(P<0.05)。模型组小鼠血清LPS水平达到(22.5±1.8)ng/mL,与对照组((13.2±3.0)ng/mL)相比显著升高(P<0.05);其空肠和结肠黏膜上皮紧密连�Objective:To investigate the effect of nicotinamide riboside(NR),a nutritional supplement,on improving depression-like behavior and intestinal mucosal permeability in mice exposed to alcohol.Methods:Thirty male C57BL/6J mice were randomly divided into three groups(with 10 mice in each group).The mice from the control and model groups were given on a daily basis 0.2 mL of normal saline intragastrically,while the mice from the NR intervention group were administered with 400 mg/kg mb of NR intragastrically every day.The mice in the model and NR treatment groups were given freshly prepared 15%alcohol solution from 8:00 a.m.to 4:00 p.m.Monday to Thursday every week,and had free access to tap water from 4:00 p.m.to 8:00 a.m.the next day,whereas the mice in the control group were given tap water all day long.Every Friday and Saturday,the mice from the three groups were cut off from any water source and every Sunday,the mice from three groups were once again given tap water to drink freely.The mice in all these groups were allowed to eat freely throughout the experiment,which lasted for 10 weeks.The depression-like behavior of the mice was evaluated by open field test,sucrose preference test and forced swimming test.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of the CA1 region of the hippocampus of mice.The serum levels of brain-derived neurotrophic factor(BDNF)and lipopolysaccharide(LPS)were measured by enzyme-linked immunosorbent assay.The ultrastructures of intercellular linkages in jejunum and colon tissues were examined using a transmission electron microscope.The permeability of jejunum and colon tissues was observed by tracer test.Western blotting was used to detect the expression of the tight junction proteins,occludin and ZO-1,in jejunum and colon tissues.Results:In the open field test,the total distance and the time spent in the central area of the model group were decreased compared with the control and NR groups.Similarly,the sucrose preference of the mice in the model group wa

关 键 词：烟酰胺核糖 酒精 小鼠 抑郁样行为 肠黏膜屏障 

分 类 号：R151.3[医药卫生—营养与食品卫生学]