远隔缺血后适应对血管性认知功能损害小鼠模型白质的保护作用

Protective effects of remote ischemic post conditioning on white matte in a mouse model of vascular cognitive impairment

目的 研究远隔缺血后适应（RIPostC）对血管性认知功能损害（VCI）保护作用。方法 将12只清洁级健康雄性C57BL／6J小鼠采用随机数字表法分为3组：假手术组（sham组，n=4），模型对照组（BCAS组，n=4）及模型-远隔缺血组（BCAS＋RIPostC组，n=4）。采用双侧颈总动脉狭窄（BCAS）制作小鼠VCI动物模型。手术后14d，BCAS＋RIPostC组小鼠双侧后肢同时进行RIPostC处理，持续5min，如此反复4次／天，持续处理2周，之后采用Morris水迷宫测试认知能力，HE染色检测各组小鼠大脑白质病理损伤情况。Western blot检测各组小鼠大脑白质组织中Beclin-1蛋白表达水平，小鼠水迷宫实验平均逃避潜伏期采用重复测量方差分析，余数据采用单因素方差分析，两两比较采用LSD-t检验。结果 28天后水迷宫测试显示，与sham组相比，BCAS组及BCAS＋RIPostC组平均逃避潜伏期延长（P〉0．05），与BCAS组相比，BCAS＋RIPostC组平均逃避潜伏期缩短（P〉0．05）。HE染色显示RIPostC可以改善BCAS所致脑白质损伤程度。Western blot显示与sham组相比BCAS组及BCAS＋RIPostC组自噬相关蛋白Beclin-1水平的表达增加（P〈0．05），BCAS＋RIPostC组Beclin-1水平的表达增加更明显（P〈0．05）。结论 RIPostC治疗可以减轻BCAS所致脑白质损伤，具有神经保护作用，该保护作用可能与自噬途径有关。

Objective To investigate the protective effect of limb remote isehemie posteonditioning （RIPostC） on vascular cognitive impairment （VCI）. Methods According to random number table, twelve healthy male C57BL / 6J mice were randomly divided into 3 groups ： sham operation group （ sham group, n = 4）, model control group （BCAS group, n = 4） and model-distal isehemia group （BCAS ＋ RIPostC group, n =4）. The bilateral carotid artery stenosis （BCAS） was used to produce mice model. Two weeks after the BCAS surgery, BCAS ＋ RIPostC mice were treated with RIPostC at the same time for 5 minutes, repeated 4 times a day for 2 weeks. And morris water maze test was used to test the cognitive function. HE staining was used to detect pathological changes of white matter in each group at the same time. The expression of Beelin-1 protein in the white matter was detected by Western blot. The repeated measurement ANOVA was used to analyse verage escape latency of mice. The remaining data were analyzed by one-way ANOVA, LSD-t test was used to compare two groups. Results Twenty eight days later , The water maze test showed that the BCAS group and the BCAS ＋ RIPostC group had a longer escape latency than the BCAS group（P 〉0.05）. Compared with the sham group, The mean escape latency of RIPostC group was shortened（P 〉 0.05）. HE staining showed that RIPostC could improve the degree of white matter damage induced by BCAS. Western blot showed that the expression of Beelin-1 in BCAS group and BCAS ＋ RIPostC group was significantly higher than that in sham group （P 〈 0.05）, and the expression of Beelin-1 in BCAS ＋ RIPostC group increased more significantly （ P 〈 0.05 ）. Conclusion RIPostC can reduce the damage of brain white matter caused by BCAS, and the neuroproteetive effect of RIPostC may be related to the autophagy pathway.