APP17肽改善糖尿病小鼠脑组织Tau蛋白过度磷酸化(英文)

Improved effect of APP17 peptide on overexpression of phosphorylated Tau protein in brain tissues of mice with diabetes mellitus

背景:Tau蛋白的过度磷酸化是痴呆的一个因素,国外学者研究发现APP17肽对其可能产生影响。目的:观察注射APP17肽后糖尿病小鼠Tau蛋白Ser202/Thr205磷酸化的变化。设计:随机对照实验。单位:首都医科大学病理学教研室,首都医科大学宣武医院脑老化研究室。材料:实验在首都医科大学病理学教研室、北京市宣武医院脑老化研究室完成。选用8周龄雄性昆明小鼠18只,体质量28～32g,随机分为3组:对照组,糖尿病组,APP17肽治疗组,每组6只小鼠。方法:用链脲佐菌素选择性地破坏胰岛β-细胞,诱发小鼠糖尿病模型,并皮下注射APP17肽给予治疗。4周后取脑组织进行AT-8(抗Ser202/Thr205特异单抗)免疫组化染色。主要观察指标:①形态学观察。②AT-8分布。③免疫组化染色定量分析。结果:糖尿病组AT-8阳性反应细胞广泛分布于压后颗粒皮层、海马、丘脑、下丘脑等部位,而对照组及APP17肽治疗组仅在压后颗粒皮层、海马可见阳性反应细胞,且着色淡。结论:糖尿病脑内多个区域的神经元可能存在较多的AT-8阳性细胞,而APP17肽可能使AT-8阳性反应细胞出现的部位和数量正常化。

BACKGROUND： Overexpression of phosphorylated Tau protein is a factor of dementia, and scholars abroad find that APP17 peptide may have effect on it. OBJECTIVE： To observe changes of phosphorylated Tau protein Ser202/ Thr205 of mice with diabetes mellitus （DM） after injection of APP17 peptide. DESIGN： Randomized control study. SETTING： Department of Pathology, Capital University of Medical Sciences; Department of Brain Aging, Xuanwu Hospital, Capital University of Medical Sciences. MATERIALS： The experiment was carried out in the Pathological Department of Capital University of Medical Sciences and Brain Aging Department of Beijing Xuanwu Hospital. A total of 18 male Kunming mice of 8 weeks old and weighing 28-32 g were randomly divided into control group, DM group and APP17 peptide group with 6 in each group. METHODS： DM models were induced by streptozotocin （STZ） through selectively destroying β-islet cells; meanwhile, APP17 peptide was intraperitoneally injected into mice. Four weeks later, brain tissue underwent immunohistochemical staining with AT-8 （Ser202/Thr205, a special monoclonal antibody）. MAIN OUTCOME MEASURES： （1） Morphological observation; （2） AT- 8 distribution; （3） quantitative analysis of immunohistochemical staining. RESULTS： Positive AT-8 cells in DM group were distributed in retrosplenial cortex, hippocampus, thalamus, hypothalamus, etc.; however, those in control and APP17 peptide groups were only distributed in retrosplenial cortex and hippocampus, and poorly stained. CONCLUSION： Positive AT-8 cells may be widely distributed in neurons of brains of DM mice; however, APP17 peptide may normalize the expression of positive AT-8 cells.