| 程 艳,李 扬,郭建伟,朱 婧,李思远,薛荣亮.SOD融合蛋白降低阿尔兹海默症小鼠脑内氧化水平及改善认知功能[J].,2022,(19):3634-3639 |
| SOD融合蛋白降低阿尔兹海默症小鼠脑内氧化水平及改善认知功能 |
| P-SOD Reduces the Level of Oxidation in the Brain and Improves Cognitive Function in AD Mice |
| 投稿时间：2022-03-07 修订日期：2022-03-31 |
| DOI：10.13241/j.cnki.pmb.2022.19.006 |
| 中文关键词: AD SOD MDA 行为学测试 |
| 英文关键词: AD SOD MDA Behavioral Test |
| 基金项目:国家自然科学基金项目（81471131） |
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| 中文摘要: |
| 摘要 目的：观察SOD融合蛋白对阿尔茨海默症（Alzheimer's Disease，AD）小鼠学习记忆能力及大脑氧化应激水平影响，探究小鼠行为改变与脑内氧化应激水平之间的关系。方法：选用32只KM雄性小鼠，适应性饲养7天后，随机分为4组：假手术组（S组），模型组（M组），SOD干预模型组（SM组）和SOD融合蛋白干预模型组（PM组）。实验第8天进行Y迷宫和黑白箱测试，9-23天，通过小鼠连续腹腔内注射等量生理盐水（S和M组）、6 mg/kg SOD（SM组）或6 mg/kg SOD融合蛋白（PM组）进行预防干预。其中，实验第16天，通过5 μL微量注射器将生理盐水（S组，2 μL/只）及Aβ1-42寡聚体（M组、SM组及PM组，2 μL/只）注射于小鼠右侧脑室，制备AD动物模型。第24天及31天进行Y迷宫和黑白箱测试。行为学测试结束后，随机选取一侧大脑半球用ELISA法测定脑组织匀浆中的SOD和MDA水平。结果：1）行为学测试：第8天，各处理组间差异无统计学意义，第24及第31天，与S组相比，M组小鼠Y迷宫新颖臂探索距离、探索次数及探索时间及黑白箱测试白箱探索距离、探索次数及探索时间均明显增加（P<0.05）；与M组相比，PM组小鼠Y迷宫新颖臂探索距离、探索次数及探索时间及白箱探索距离、探索次数及探索时间均明显减少（P<0.05）；SM组与M组相比差异无统计学意义。2）小鼠脑组织匀浆中SOD和MDA测定：与S组相比，M组SOD活性明显下降而MDA表达明显升高（P<0.05），与M组相比，PM组SOD活性明显增加而MDA表达明显下降（P<0.05），SM组与M组相比差异无统计学意义。3）SOD活性与Y迷宫新颖臂探索距离、探索次数和探索时间以及黑白箱中白箱探索距离、探索次数和探索时间呈负相关，而MDA表达与Y迷宫新颖臂探索距离、探索次数和探索时间以及黑白箱中白箱探索距离、探索次数和探索时间呈正相关。结论：SOD融合蛋白腹腔内注射可明显减轻Aβ1-42诱导的氧化应激及改善AD小鼠的行为恶化。SOD融合蛋白的抗氧化功能可能是预防AD的有效方法。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the P-SOD's effects on behavior and cerebral oxidative stress in AD mice, and to analyze the relationship between changes in mouse behavior and levels of brain oxidation and antioxidant. Methods: 32 KM male mice were used for adaptive breeding for 7 days. The mice were randomly divided into 4 groups: sham operation group (group S), model group (group M), SOD intervention model group (group SM), and P-SOD intervention model group (group PM). After 7 days normal feeding for adaptation, mice from these four groups were intraperitoneally injected daily for 14 days: group S and M with normal saline; group SM with 6 mg/kg SOD, group PM with 6 mg/kg pETl6b-PTD4-Cu, Zn-SOD. On the 8th day of intraperitoneal injection, after locating the right lateral ventricle of mice by the stereotaxic apparatus, 2 μL of normal saline was injected into lateral ventricle in mice from group S, whereas 2 μL of Aβ1-42 oligomer (1 μg/mL) was injected into lateral ventricle in mice from other groups. The Y-maze and the light-dark box test performed on the 8th, 24th and 31st day respectively. After the behavior test, animals were sacrificed and the fresh tissue of one cerebral hemisphere was taken for SOD and MDA determination. Results: 1) Behavioral tests: There was no statistical difference in distance, duration and numbers of visits in novel arm of Y-maze test and in light box of Light-dark box test between mice from different groups on the 8th day. However, on the 24th and 31th day, mice in group M showed significantly increased with those above when compared with the group S(P<0.05). Differently, mice in group PM showed significantly decreased with those above when compared with those from group M(P<0.05). 2) Compared with group M, mice in group S and PM showed significantly higher SOD but lower MDA levels in brain tissue(P<0.05). 3) Correlation analysis between SOD/MDA expression and behavioral performance showed SOD levels negatively, whereas MDA positively correlated with visiting distance, number and duration in Y-maze novel arm and light box. Conclusion: P-SOD intraperitoneal injection can alleviate Aβ+-induced oxidative stress and improve behavioral deterioration in AD mice. The antioxidant function of P-SOD may be an effective method to prevent AD. |
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