短期自愿运动对高脂血症小鼠脑出血后内源性神经干细胞的影响  

Short-term voluntary exercise enhances the activation of endogenous neural stem cells inintracerebral hemorrhage mice with hyperlipidemia

作　　者：胡晓宣 刘倩[1] 王童卓 孙美琪 张子宣 黄鹏瑜 罗宇佳 王飔 吕海侠[1] HU Xiaoxuan;LIU Qian;WANG Tongzhuo;SUN Meiqi;ZHANG Zixuan;HUANG Pengyu;LUO Yujia;WANG Si;L Haixia(Department&Institute of Neurobiology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center;Department of Human Anatomy&Histoembryology,School of Basic Medical Sciences;The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学基础医学院神经生物学系 [2]西安交通大学基础医学院人体解剖与组织胚胎学系 [3]西安交通大学第一附属医院,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2023年第3期396-402,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金面上项目(No.82171389)。

摘　　要：目的探究短期自愿运动对高脂血症小鼠脑出血(intracerebral hemorrhage,ICH)后神经功能修复和内源性神经干细胞(endogenous neural stem cells,eNSCs)激活的影响。方法4月龄Nestin-CreERT2:tdTomato转基因C57BL/6雄性小鼠,8周高脂饮食(high fat diet,HFD)喂养后,立体定位仪辅助下纹状体注射Ⅳ型胶原酶,构建ICH模型。ICH后2 d小鼠开始自主转轮运动,连续7 d;在运动第1、3、5、7天采用NSS、Beam walking实验评估小鼠神经功能;脑组织免疫荧光染色观察侧脑室下区Nestin、Ki67和DCX阳性细胞数量,评估eNSCs激活。结果①与正常饮食(chow diet,CD)组相比,HFD组小鼠8周后体质量、血糖、血清脂质代谢相关因子浓度明显升高,肝脏组织Nile Red染色阳性细胞明显增加。②与假手术(Sham)组相比,ICH组小鼠NSS评分明显升高、Beam walking距离缩短。运动(Ex)组小鼠NSS评分较非运动组下降、Beam walking距离增加,7 d后与Sham组无统计学差异。③与Sham组相比,ICH组小鼠Nestin^(+)/Ki67^(+)细胞数量减少,Nestin^(+)/DCX^(+)细胞数量增加。运动组小鼠Nestin^(+)/Ki67^(+)及Nestin^(+)/DCX^(+)细胞数量均较Sham组明显增加,运动组间无统计学差异;与ICH组相比,运动后(ICH^(+)Ex)Nestin^(+)/DCX^(+)细胞数量差异无统计学意义。结论损伤急性期启动短期自愿运动可改善高脂血症小鼠ICH后神经功能,促进eNSCs激活,为进一步开发基于eNSCs的ICH加速康复策略提供了新的思路。Objective To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells(eNSCs)via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage(ICH).Methods Four-month-old male Nestin-CreERT2:tdTomato transgenic mice were fed with high-fat diet(HFD)for eight weeks.TypeⅣcollagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus.Voluntary exercise(wheel running)was initiated on the second day after ICH and monitored daily for seven days.Neurological severity score(NSS)and beam walking test were applied to evaluate motor function and coordination.Liver and brain tissues were collected at day 9 after ICH and sliced for staining.Then the Nestin-labeled cells,Ki67^(+),and doublecortin(DCX)^(+)in subventricular zone(SVZ)were counted to evaluate eNSCs activation.Results①Compared with those of mice fed by chow diet(CD),the body weight,blood glucose level,concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice,confirming hyperlipidemia.②Compared with the sham group,NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased,showing the deficiency of motor function.It could be rescued by 7-day wheel running,as shown by a lower NSS score and a longer cross-beam walking distance.③Compared with the sham group,the number of Nestin^(+)/Ki67^(+)cells decreased and Nestin^(+)/DCX^(+)cells increased after ICH.After 7-day voluntary exercise,the number of Nestin^(+)/Ki67^(+)cells decreased but that of Nestin^(+)/DCX^(+)cells further increased significantly.However,compared with ICH,the increase of Nestin^(+)/DCX^(+)cells in ICH^(+)Ex was not significant.Conclusion Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia.This provides a new idea for further developing ICH ac

关 键 词：脑出血 高脂血症 自愿运动 内源性神经干细胞 

分 类 号：R743.34[医药卫生—神经病学与精神病学]