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miR-10b-5p 抑制物通过 Rho/ROCK 信号通路上调 HOXD10 减轻大鼠阿尔茨海默病。

Inhibition of microRNA-10b-5p up-regulates HOXD10 to attenuate Alzheimer's disease in rats via the Rho/ROCK signalling pathway.

机构信息

Department of Neurology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.

Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China.

出版信息

J Drug Target. 2021 Jun;29(5):531-540. doi: 10.1080/1061186X.2020.1864739. Epub 2021 Jan 11.

Abstract

OBJECTIVE

It is believed that microRNAs (miRNAs) participate in the pathogenesis of Alzheimer's disease (AD), but the specified function of miR-10b-5p in the disease has not been thoroughly understood. Thereafter, this research aimed to assess the function of miR-10b-5p in AD.

METHODS

Rat AD models were established by injected with amyloid-β (Aβ), which were mainly treated with lentivirus-miR-10b-5p inhibitor, or lentivirus-overexpressed homeobox D10 (HOXD10). MiR-10b-5p, HOXD10, RhoA, ROCK1 and ROCK2 expression in rat hippocampal tissues were determined. Afterwards, the behaviour of rats was tested, and neuronal apoptosis, pathological injury, and inflammatory factors and oxidative stress-related factors were all assessed. Finally, the target relation between miR-10b-5p and HOXD10 was detected.

RESULTS

MiR-10b-5p was upregulated while HOXD10 was downregulated, and the Rho/ROCK signalling pathway was activated in hippocampal tissues of rats with AD. Inhibition of miR-10b-5p could attenuate the neuronal apoptosis, pathological injury, inflammation reaction, and oxidative stress by elevating HOXD10 and inhibiting the Rho/ROCK signalling pathway in AD rats. Moreover, HOXD10 was targeted by miR-10b-5p.

CONCLUSION

Inhibited miR-10b-5p decelerated the development of AD by promoting HOXD10 and inactivating the Rho/ROCK signalling pathway, and our findings may contribute to the exploration of AD treatment.

摘要

目的

据信 microRNAs(miRNAs)参与阿尔茨海默病(AD)的发病机制,但 miR-10b-5p 在该疾病中的特定功能尚未被充分理解。因此,本研究旨在评估 miR-10b-5p 在 AD 中的功能。

方法

通过注射淀粉样蛋白-β(Aβ)建立大鼠 AD 模型,主要用慢病毒-miR-10b-5p 抑制剂或慢病毒过表达同源盒 D10(HOXD10)进行处理。测定大鼠海马组织中 miR-10b-5p、HOXD10、RhoA、ROCK1 和 ROCK2 的表达。随后,对大鼠的行为进行测试,并评估神经元凋亡、病理损伤以及炎症因子和氧化应激相关因子。最后,检测 miR-10b-5p 和 HOXD10 之间的靶关系。

结果

AD 大鼠海马组织中 miR-10b-5p 上调,HOXD10 下调,Rho/ROCK 信号通路被激活。抑制 miR-10b-5p 可通过上调 HOXD10 和抑制 AD 大鼠中的 Rho/ROCK 信号通路来减轻神经元凋亡、病理损伤、炎症反应和氧化应激。此外,HOXD10 是 miR-10b-5p 的靶标。

结论

抑制 miR-10b-5p 通过促进 HOXD10 和失活 Rho/ROCK 信号通路来减缓 AD 的发展,我们的研究结果可能有助于 AD 治疗的探索。

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