scFv17改善12月龄三转基因小鼠步态的作用

doi:10.12047/j.cjap.5656.2018.089

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (5): 389-395.doi: 10.12047/j.cjap.5656.2018.089

scFv17改善12月龄三转基因小鼠步态的作用

王婷, 曹越, 胡梦明, 张秀敏, 董雪帆, 祁金顺, 张军, 杨威

山西医科大学生理学系, 细胞生理学省部共建教育部重点实验室, 太原 030001

收稿日期:2017-11-27 修回日期:2018-07-28 出版日期:2018-09-28 发布日期:2019-02-21
通讯作者: 杨威,Tel:13293910485;E-mail:vividmail@163.com E-mail:vividmail@163.com
基金资助:
山西省留学回国留学人员科研资助项目（2016-060）

The improvement effect of scFv17 on the gait of triple-transgenic mice

WANG Ting, CAO Yue, HU Meng-ming, ZHANG Xiu-min, DONG Xue-fan, QI Jin-shun, ZHANG Jun, YANG Wei

Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China

Received:2017-11-27 Revised:2018-07-28 Online:2018-09-28 Published:2019-02-21
Supported by:
山西省留学回国留学人员科研资助项目（2016-060）

摘要/Abstract

摘要： 目的：观察PS1M146V/APPswe/tauP301L三转基因阿尔茨海默病（AD）（3xTg-AD）模型小鼠的步态改变以及探究scFv17对其的改善作用。方法：本实验首先选用6月龄3xTg-AD小鼠（n=18）和C57BL/6野生型（WT）小鼠（n=24），观察记录它们的步态行为，在12月龄时发现3xTg-AD小鼠的步态严重受损后，将上述两种小鼠随机分为野生型对照组（WT+PBS）（n=12）、野生型给药组（WT+scFv17）（n=12）、3xTg-AD对照组（3xTg-AD+PBS）（n=9）以及3xTg-AD小鼠给药组（3xTg-AD+scFv17）（n=9）四组。采用鼻饲方法，每次给予每只小鼠20 μl的scFv17（1.5 mg/kg）或者等体积的PBS （0.01 mol/L），每周两次，连续给药12周后进行步态行为测试及小脑病理学检测。结果：与同月龄野生型小鼠比较，12月龄3xTg-AD小鼠后爪步幅宽度增大（P<0.01），摇摆时间百分比减小（P< 0.01），站立时间百分比增大（P<0.01），运动协调和平衡能力严重受损；scFv17可改善12月龄3xTg-AD小鼠运动协调和平衡能力（P<0.01），改善3xTg-AD小鼠小脑浦肯野细胞的形态结构，增多3xTg-AD小鼠小脑浦肯野细胞的尼氏小体（P<0.01），减少3xTg-AD小鼠小脑皮层内淀粉样β蛋白（Aβ）斑块和浦肯野细胞胞内神经原纤维缠结（NFT）（P<0.01）。结论：3xTg-AD小鼠在12月龄时的运动协调和平衡能力明显受损，给予scFv17可明显改善12月龄3xTg-AD小鼠的步态紊乱，其作用机制可能与改善小脑浦肯野细胞结构与蛋白功能，减少Aβ斑块和NFT有关。

关键词: 3xTg-AD小鼠, 步态, 小脑, scFv17

Abstract: Objective: To observe the gait changes of Alzheimer's disease PS1M146V/APPswe/tauP301L triple-transgenic (3xTg-AD) mice and to investigate the improvement effect of single chain variable domain antibody fragment 17 (scFv17) on the gait.Methods: In the present study, a selection of 6-month-old 3xTg-AD mice (n=18) and C57BL/6 wild-type mice (n=24) was performed. First, we observed their gait changes and found that the gait of 12-month-old 3xTg-AD mice was severely damaged. Then, the two groups of mice were randomly divided into four groups:WT+PBS(n=12), WT+scFv17(n=12), 3xTg-AD+PBS(n=9) and 3xTg-AD+scFv17(n=9). The gait behavior test and pathological test were performed after 12 weeks'continuous administration of scFv17 (1.5 mg/kg) or an equal volume of PBS (0.01 mol/L) by nasal gavage twice a week. Results: Compared with the same month old wild type mice, the rear track width of 12 month old 3xTg-AD mice was increased(P<0.01), swing time percent was decreased (P<0.01), stance time percent was increased(P<0.01), so the ability of movement coordination and balance was seriously damaged. ScFv17 could improve the coordination and balance ability of 12 month old 3xTg-AD mice(P<0.01). The morphological structure of 3xTg-AD mice cerebellar Purkinje cells was improved. The treatment of scFv17 increased the Nissl body number of the cerebellar Purkinje cells of 3xTg-AD mice (P<0.01). scFv17 reduced the amyloid β protein (Aβ) plaques in the cerebellar cortex of 3xTg-AD mice (P<0.01), and scFv17 reduced the intracellular neurofibrillary tangles (NFT) of the cerebellar Purkinje cells of the 3xTg-AD mice (P<0.01). Conclusion: The coordination and balance ability of 3xTg-AD mice was significantly impaired. ScFv17 can improve gait behaviour in the 3xTg-AD significantly.The mechanism may be related to the improvement of the structure and protein function of cerebellar Purkinje cells, and the eliminating of the Aβ plaques and the neurofibrillary tangles.

Key words: 3xTg-AD mice, gait, cerebellum, scFv17

王婷, 曹越, 胡梦明, 张秀敏, 董雪帆, 祁金顺, 张军, 杨威. scFv17改善12月龄三转基因小鼠步态的作用[J]. 中国应用生理学杂志, 2018, 34(5): 389-395.

WANG Ting, CAO Yue, HU Meng-ming, ZHANG Xiu-min, DONG Xue-fan, QI Jin-shun, ZHANG Jun, YANG Wei. The improvement effect of scFv17 on the gait of triple-transgenic mice[J]. CJAP, 2018, 34(5): 389-395.

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scFv17改善12月龄三转基因小鼠步态的作用

The improvement effect of scFv17 on the gait of triple-transgenic mice

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