Abstract:
Objective To evaluate the imaging changes in patients with cerebral small vessel disease(cSVD) and the risk factors of Alzheimer's disease(AD). Methods Retrieve relevant retrospective case analysis and observational studies that about cSVD and the risk factors of AD from online database (January 1, 1980-April 1, 2019) as PubMed, EMBASE/SCOPUS and Cochrane Library with key words: Alzheimer's disease, cerebral small vessel disease, white matter lesion, cerebral microbleeds, lacunar infarction. Selection of studies was performed according to pre-designed inclusion and exclusion criteria. Quality of studies was evaluated by using Newcastle-Ottawa Scale (NOS). All data were pooled by Stata 15.1 software for Meta-analysis. Results A total of 1452 articles were enrolled, from which 11 studies with NOS score≥5 were chosen after excluding duplicates and those not meeting the inclusion criteria. A total of 12882 patients were included. Meta-analysis showed that white matter lesion (RR=1.152,95%CI: 1.007-1.317; P=0.039) and cerebral microbleeds (RR=1.659, 95%CI: 1.085-2.537; P=0.019)increased the risk of AD;lacunar infarc did not increase the risk of AD(RR=1.298,95%CI:0.785-2.147; P=0.309). Conclusions The risk of Alzheimer's disease is increased in patients with white matter lesion and cerebral microbleeds. The cerebral small vessel disease may be involved in the occurrence of some Alzheimer's disease. When patients have the imaging changes of white matter lesion and cerebral microbleeds, should be paid on primary prevention of Alzheimer's disease.
Key words:
Cerebral small vessel diseases,
Alzheimer disease,
Magnetic resonance imaging,
Meta-analysis
摘要： 目的 探讨褪黑素对脑小血管病模型大鼠社交行为和脑白质损害的改善作用及其药理学机制。方法 采用双侧颈总动脉结扎法制备慢性脑低灌注模型，44只SD大鼠随机分为假手术组、模型组、褪黑素5mg/（kg·d）组和10mg/（kg·d）组（每组各11只），分别以嗅探实验（嗅探时间和穿越次数）评价模型大鼠社交行为、倒置相差荧光显微镜观察胼胝体髓鞘碱性蛋白（MBP）表达水平、透射电子显微镜观察胼胝体白质髓鞘完整性（即G-ratio）、Western blotting法测定磷酸化哺乳动物雷帕霉素靶蛋白（pmTOR）/哺乳动物雷帕霉素靶蛋白（mTOR）比值。结果 与假手术组相比，模型组大鼠嗅探时间（t= 58.000， P=0.000）和穿越次数（t=20.000， P=0.000）减少，胼胝体MBP阳性细胞数目减少（t=20.400， P=0.000）、 G-ratio表达水平升高（t=-9.800， P=0.025）、pmTOR/mTOR比值降低（t=20.336， P=0.000）；予褪黑素［5或10mg/（kg·d）］治疗后，大鼠嗅探时间（t=-12.600， P=0.001； t=-26.000， P=0.000）和穿越次数 （t=-8.400， P=0.000； t=-10.200， P=0.000）、胼胝体pmTOR/mTOR比值（t=-6.022， P=0.014； t=-8.800， P=0.001）高于模型组但仍低于假手术组（t=45.000， P=0.000； t=32.000， P=0.000； t=11.600， P=0.000； t=9.800， P=0.000； t=14.314， P=0.000； t=11.536， P=0.000），同时胼胝体MBP阳性细胞数目亦增加（t= -16.800， P=0.001； t=-20.600， P=0.000）、 G-ratio表达水平降低（t=8.600， P=0.041； t=9.200， P=0.030） 但接近假手术组水平（均P>0.05）；褪黑素10mg/（kg·d）组大鼠嗅探时间延长并且高于5mg/（kg·d）组 （t=-13.400， P=0.000）。结论 褪黑素可以有效改善脑小血管病模型大鼠社交行为、减轻脑白质损害， 其机制可能与提高mTOR磷酸化水平有关。
关键词:
大脑小血管疾病,
褪黑激素,
白质,
疾病模型,
动物