APP17肽改善糖尿病小鼠脑组织Tau蛋白过度磷酸化(英文)

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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: Hyperphosphorylation of Tau protein is a factor of dementia. Studies abroad have found that APP17 peptide may have an impact on it. Objective: To observe the phosphorylation of Tau protein Ser202 / Thr205 in diabetic mice after injection of APP17 peptide. Design: Randomized controlled experiment. SETTING: Department of Pathology, Capital Medical University, Brain Aging Laboratory, Xuanwu Hospital, Capital Medical University. Materials: The experiment was performed at the Pathology Department of Capital Medical University and the Brain Aging Laboratory of Xuanwu Hospital in Beijing. Eighteen male Kunming mice of 8 weeks old were randomly divided into 3 groups: control group, diabetes group and APP17 peptide treatment group, 6 mice in each group. Methods: Pancreatic islet β-cells were selectively destroyed by streptozotocin. Mouse diabetic model was induced and APP17 peptide was injected subcutaneously for treatment. After 4 weeks, the brain tissue was harvested for AT-8 (anti-Ser202 / Thr205 specific mAb) immunohistochemical staining. MAIN OUTCOME MEASURES: ① Morphological observation. ②AT-8 distribution. ③ immunohistochemistry quantitative analysis. Results: AT-8 positive cells in diabetic group were widely distributed in the granule cortex, hippocampus, thalamus, hypothalamus and other parts of the diabetic group, but in the control group and the APP17 peptide-treated group, positive cells were observed in the cortex and hippocampus only. light. CONCLUSIONS: There are many AT-8 positive neurons in multiple regions of brain of diabetic patients, while APP17 peptide may normalize the location and number of AT-8 positive cells.
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