非肥胖型糖尿病小鼠成年神经发生的实验研究  

Study on Adult Neurogenesis in an Animal Model of Non-obese Diabetes

作　　者：党丹[1] 吴芳[1] 郭俊[1] 李宏增[1] 赵聪[1] 汪杰[1] 李川[1] 李柱一[1] 

机构地区：[1]第四军医大学唐都医院神经内科,陕西西安710038

出　　处：《现代生物医学进展》2014年第29期5605-5608,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(31200665)

摘　　要：目的:探讨异常免疫反应介导的糖尿病(DM)对大脑神经干/祖细胞(NSC/NPC)增殖的影响。方法:依据尿糖测定结果将非肥胖型糖尿病(NOD)小鼠分为发病组和未发病组,观察两组小鼠的体重变化和胰岛炎的严重程度。通过5-溴-2'-脱氧尿苷(BrdU)掺入和免疫荧光染色方法,观察两组小鼠海马齿状回(DG)和侧脑室下区(SVZ)的BrdU阳性细胞数量的变化,以评估NSC/NPC增殖情况。结果:发病组小鼠呈现出多饮、多食、多尿等糖尿病典型症状,体重较未发病组明显减低。发病组小鼠胰腺组织中炎症评分为3分的胰岛数量明显多于未发病组,且胰岛炎症的平均评分显著高于未发病组(P<0.05)。与未发病组比较,发病组小鼠大脑海马DG区BrdU阳性细胞显著降低(P<0.01);SVZ区的BrdU阳性细胞数量亦明显少于未发病组(P<0.001)。结论:异常免疫反应介导的DM可抑制小鼠大脑NSC/NPC的增殖。Objective： To investigate the changes of the proliferation of neural stern/progenitor cell （NSC/NPC） in diabetes mellitus （DM） mediated by abnormal immune responses. Methods： Female non-obese diabetic （NOD） mice were divided into non-DM or DM groups according to the results of glycosuria tests. The changes of body weight and the severity of insulitis were observed and compared between the two groups. 5-bromo-2＇-deoxyuridine （BrdU） incorporation and subsequent BrdU immunofluorescent staining were used. The NSC/NPC proliferation was assessed by counting the number of BrdU-positive ceils in the dentate gyrus （DG） of hippocampus and in the subventricular zone （SVZ）, respectively. Results： Diabetic NOD mice exhibited the classical symptoms of hyperglycemia including polydipsia, polyuria, and weight loss. The number of islets with an inflammatory score of 3 was larger in DM group than in non-DM group. The mean inflammatory score of insulitis is also higher in DM group （P 〈 0.05）. Compared with non-DM NOD mice, the number of BrdU-positive ceils was significantly decreased in the DG of hippocampus in diabetic NOD mice （P〈0.01）. Similarly, a reduced number of BrdU-positive cells also occurred in the SVZ of diabetic NOD mice （P〈0.001）. Conclusion： Abnormal immune responses-mediated DM contributes to an impaired NSC/NPC proliferation in female NOD mice.

关 键 词：糖尿病 非肥胖型 神经干 祖细胞 增殖 

分 类 号：R587.1[医药卫生—内分泌]