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目的:分析糖尿病性认知功能障碍（DACD）大鼠脑白质差异蛋白质组学。方法:20只SD大鼠分为对照组（10只）和2型糖尿病（T2DM）组（10只），对照组喂养标准饲料，T2DM组利用高脂高糖饮食联合腹腔注射链脲霉素建立T2DM模型。利用Morris水迷宫检测大鼠认知功能，使用弥散张量成像技术评价大鼠脑白质病变（WML）程度。通过蛋白质非标记定量技术（Label-free）进行脑白质差异蛋白质组学分析，对筛选出的差异蛋白质进行生物信息学分析，最后选取一些差异蛋白质进行Western blot验证。组间差异的比较采用独立样本n t检验或Wilcoxon检验。n 结果:共筛选到38种差异蛋白质：24个蛋白表达上调（差异倍数>2.0且n P<0.05），14个蛋白表达下调（差异倍数<-2.0且n P2.0 andn P<0.05) and 14 down-regulated proteins (fold change<-2.0 andn P<0.05). The differential proteins mainly distributed in cell membrane, cytoplasm and exosomes. And they were mainly involved in biological processes such as nervous system development, negatively regulating apoptosis of neural cells, and chemical synaptic transmission. The varied proteins were mainly concentrated on the four signal pathways, moreover, brain-derived neurotrophic factor, nitric oxide synthase 1, neuromodulin (GAP43), vesicular glutamate transporter 1 (SLC17A7), dynamin-1, metabotropic glutamate receptor 5 and amino acid transporter would be core backbones of the protein complexes to form interactive network.n Conclusions:The differentially proteomics are involved in multiple signal pathways of cognitive dysfunction and WML. GAP43 and SLC17A7 may be the crucial targets of WML.