胰高血糖素样肽1受体激动剂对阿尔茨海默病鼠脑结构影响的Meta分析

The effect of glucagon-like peptide 1 receptor agonists on brain structure in rat or mouse Alzheimer’s disease models:a Meta-analysis

目的系统评价胰高血糖素样肽1受体激动剂(GLP-1RA)对阿尔茨海默病(AD)大(小)鼠脑结构的影响。方法计算机检索自建库至2018年1月Cochrane Library、EMbase、PubMed、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、中文科技期刊全文数据库维普(VIP)、万方数据库(WFSD)发表的以GLP-1受体激动剂对AD大(小)鼠脑结构影响的随机对照试验(RCT),设立纳入与排除标准筛选文献,根据SYRCLE动物实验偏倚风险评估工具进行质量评价后,提取数据并采用RevMan 5.3软件进行Meta分析。结果共纳入文献9篇,207只大、小鼠,其中试验组123例,对照组84例。Meta分析结果显示,使用GLP-1RA治疗后,大(小)鼠大脑内淀粉样斑块负荷[低剂量组:平均差(MD)=-5.55,95%CI:-6.92^-4.17,P<0.01,高剂量组:MD=-4.81,95%CI:-6.63^-2.98,P<0.01]、p-tau蛋白数(MD=-3.16,95%CI:-4.29^-2.02,P<0.01)及大脑小胶质细胞激活数(利拉鲁肽治疗组:MD=-7.85,95%CI:-12.66^-3.04,P<0.01,利西拉肽治疗组:MD=-7.60,95%CI:-9.56^-5.65,P<0.01),均低于对照组,其差异有统计学意义(均P<0.05)。结论GLP-1RA可减少大(小)鼠大脑淀粉样斑块负荷、神经纤维缠结数及减少大(小)鼠大脑小胶质细胞激活数。

Objective To systematically evaluate the effect of glucagon-like peptide 1 receptor agonists(GLP-1RA)on the brain structure of rat or mouse Alzheimer’s disease(AD)models.Methods Data of randomized controlled trials from January 2000 to January 2018 for the effect of GLP-1RA on the brain structure of AD rats or mice were searched from all databases,including the Cochrane Library,EMbase,PubMed,Chinese Journal Full-text Database,the Chinese biomedical literature database,Chinese PSTP VIP and Wanfang database.Literature was selected based on inclusion and exclusion criteria defined in advance,and the quality was evaluated using the SYRCLE as animal experimental bias risk assessment tools.Valid data were retrieved and a meta-analysis was performed using the RevMan 5.3software.Results A total of 9 articles with 207 rats and mice were included.Among the 207 cases,123cases were in the experimental group and 84 cases in the control group.After treatment with GLP-1RA,there were significant differences in the amyloid plaque load[Low dose group:mean difference(MD)=-5.55,95%CI:-6.92 to-4.17,P<0.01,High dose group:MD=-4.81,95%CI:-6.63to-2.98,P<0.01],the amount of p-tau protein(MD=-3.16,95%CI:-4.29 to-2.02,P<0.01),and the activation of microglia in rat or mouse brain(liraglutide treatment group:MD=-7.85,95%CI:-12.66 to-3.04,P<0.01,lixisenatide treatment group:MD=-7.60,95%CI:-9.56 to-5.65,P<0.01)between the treatment group and the control group.Conclusions GLP-1RA can reduce the amyloid plaque load,decrease the number of neurofibrillary tangles and inhibit the activation of microglia in the rat or mouse brain.