| 陈红媛 王永闯 李立 王莉 俞春江.β-分泌酶抑制剂对tau 过磷酸化大鼠β-CTF代谢的影响及机制研究[J].,2017,17(2):237-241 |
| β-分泌酶抑制剂对tau 过磷酸化大鼠β-CTF代谢的影响及机制研究 |
| The Effects and Mechanisms of β-secretase Inhibitor on the Processing ofβ-CTF in Tau Hyperphosphorylated Rat Model |
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| DOI： |
| 中文关键词: 阿尔茨海默病 淀粉样前体蛋白C末端片段 BACE1 tau 过磷酸化 |
| 英文关键词: Alzheimer's disease Amyloid C-terminal fragment of amyloid precursor protein BACE1 Tau hyperphosphorylation |
| 基金项目:黑龙江省卫生计生委科研基金项目(2014-337)；黑龙江省博士后基金项目(LBH-Z15135) |
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| 中文摘要: |
| 目的：在tau 过磷酸化大鼠中，通过检测淀粉样前体蛋白(amyloid precursor protein, APP)C末端片段的表达，研究抑制β- 分
泌酶(BACE1)对其代谢的影响及机制。方法：24 只SD大鼠随机分为四组，包括正常对照组、假手术组、OA 组、OA+BACE1 抑制剂
组。Western blot 法检测β-CTF、APP 及BACE1 表达；RT-PCR 法检测APP 及BACE1；水迷宫检测大鼠行为学。结果：OA 组
β-CTF表达显著增加(p<0.05)，而OA+BACE1 抑制剂组与OA 组相比，β-CTF表达减少(p<0.05)；四组大鼠的APP在蛋白及
mRNA 水平表达无显著差别(p＞0.05)；OA组BACE1 在蛋白及mRNA 水平的表达增加，而OA+BACE1 抑制剂组BACE1 的蛋
白表达较OA组减少(p<0.05)，两组大鼠mRNA 表达水平无明显差异(p＞0.05)。OA+BACE1 抑制剂组大鼠在给予BACE1 抑制剂
后行为学有所改善(p<0.05)。结论：⑴tau 过磷酸化通过促进神经元内BACE1 表达，导致APP代谢途径发生转变，从而引起茁-CTF
表达增加；⑵β-CTF表达增加可引起tau 过磷酸化大鼠行为学改变；⑶抑制BACE1 可改善大鼠的学习及记忆能力，支持BACE1
作为AD的治疗靶点。 |
| 英文摘要: |
| Objective:To study the effects and mechanisms of β-secretase inhibitor on the processing of β-CTF in tau
hyperphosphorylated rat model.Methods:Twenty-four male SD rats were randomly divided into four groups, including the control group,
the sham group, the OA group and the OA+BACE1 group. For each group of rats, Western blot was used to analyze the level of amyloid
precursor protein C-terminal fragment (APP-CTF), APP and BACE1. Meanwhile, RT-PCR was performed to detect the mRNA levels of
APP and BACE1. With water maze test, abilities of learning and memory were detected.Results:It was found that β-CTF significantly
increased in the OA group(p<0.05), while decreased in the OA + BACE1 inhibitor group compared to the OA group(p<0.05). There was
no statistically significant difference in the protein and mRNA levels of APP among the four groups (p>0.05). The protein and mRNA
levels of BACE1 significantly increased in the OA group (p<0.05). The protein levels of BACE1 in the OA+BACE1 inhibitor group
decreased compared to the control group (p <0.05), and there was no difference in the mRNA levels between the two groups (p> 0.05).
With water maze test, the behavior of rats in the OA+BACE1 inhibitor group were restored(p<0.05).Conclusion:⑴Hyperphosphorylated
tau protein induced the increase of BACE1 expression, thus the pathway of APP processing had been shifted, and the level of β-CTF
increased in neurons, ⑵The increase of β-CTF impaired the behavior of rats, ⑶ Inhibition of BACE1 could improve the abilities of study
and memory in rats, indicating that BACE1 might be a therapeutic target of AD. |
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