2020 年第 10 期 第 15 卷

阿尔茨海默病小鼠脑组织中微小RNA-129和淀粉样前体蛋白水平异常导致认知功能损伤的机制研究

Mechanism of cognitive impairment caused by abnormal levels of microRNA-129 and amyloid precursor proteins in Alzheimer′s disease mice

作者：玛依拉·吐尔逊殷立新阿加尔·木合大

英文作者：Mayila Tuerxun Yin Lixin Ajiaer Muheda

单位：新疆医科大学第一附属医院神经内科，乌鲁木齐830000

英文单位：Department of Neurology the First Affiliated Hospital of Xinjiang Medical University Urumqi 830000 China

关键词：阿尔茨海默病；微小RNA-129；淀粉样前体蛋白；认知功能

英文关键词：Alzheimer′sdisease;MicroRNA-129;Amyloidprecursorprotein;Cognitivefunction

• 摘要：

• 目的 探讨阿尔茨海默病（AD）小鼠脑组织中微小RNA（miR）-129和淀粉样前体蛋白（APP）水平异常导致认知功能损伤的机制。方法将80只6～8周ICR雄性小鼠完全随机分为正常组、模型组、观察组和对照组，各20只。模型组、观察组、对照组小鼠采用单侧脑室注射5 g/L脂多糖3 μl/只的方法构建AD小鼠模型，正常组小鼠注射等容量的0.9%氯化钠注射液。注射完毕后2 h，观察组、对照组小鼠分别单侧脑室注射miR-129-mimic 20 μmol/L和miR-129-mimic-NC 20 μmol/L，正常组、模型组小鼠注射等容量的0.9%氯化钠注射液。尼氏染色检测各组小鼠脑组织中神经元的损伤，免疫组化检测各组小鼠脑组织中APP的表达，荧光素酶报告基因分析miR-129和APP的关系。结果 模型组小鼠脑组织内APP蛋白相对表达量明显高于正常组［(5.68±0.38)比（1.01±0.05）］，差异有统计学意义（P＜0.05）；对照组小鼠脑组织内APP蛋白相对表达量(5.35±0.61)与模型组相比差异无统计意义（P＞0.05）；观察组小鼠脑组织内APP蛋白相对表达量（2.13±0.33）明显低于模型组，差异有统计学意义（P＜0.05）。荧光素酶报告基因分析证明miR-129靶向调控APP的表达。结论 miR-129和APP在AD小鼠脑组织中存在表达异常的现象。miR-129对AD的神经保护作用可能是通过调控APP的表达实现的。

• Objective To investigate the mechanism of cognitive impairment caused by abnormal levels of microRNA(miR)-129 and amyloid precursor proteins(APP) in Alzheimer′s disease(AD) mice. Methods Eighty institute of cancer research(ICR) male mice aged 6-8 weeks were randomly divided into normal group, model group, observation group and control group, with 20 mice in each group. The mice in the model group, observation group and control group were injected with 5 g/L lipopolysaccharide in a single at a dose of 3 μl/mouse to construct a mouse model of AD. Mice in the normal group were injected with 0.9% sodium chloride injection. After 2 h of injection, mice in observation group and control group were injected with 20 μmol/L miR-129-mimic and miR-129-mimic-NC in one ventricle respectively. Mice in the normal group and model group were injected with 0.9% sodium chloride injection of the same dose. Neuron damage in the brain tissues was detected by Nisier staining, APP expression was detected by immunohistochemistry, and the relationship between miR-129 and APP was analyzed by luciferase reporter gene. Results The relative expression of APP in the brain tissue of the model group was significantly higher than that in the normal group［(5.68±0.38) vs (1.01±0.05), P<0.05］. There was no statistically significant difference in APP protein expression between the control group (5.35±0.61) and the model group (P>0.05). The expression of APP protein in the brain tissue of the observation group was significantly lower than that of the model group［(2.13±0.33) vs (5.68±0.38),P<0.05］. Luciferase reporter gene analysis demonstrated that miR-129 targeted the regulation of APP expression. Conclusions MiR-129 and APP are abnormally expressed in the brain tissue of AD mice. The neuroprotective effect of miR-129 on AD may be achieved by regulating the expression of APP.