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小檗碱通过调节阿尔茨海默病中的 miR-188/NOS1 减轻 Aβ诱导的神经元损伤。

Berberine attenuates Aβ-induced neuronal damage through regulating miR-188/NOS1 in Alzheimer's disease.

机构信息

Department of Psychiatry, Mental Health Center of Qingdao, Qingdao University, No. 299 Nanjing Road, Qingdao, 266033, Shandong, China.

出版信息

Mol Cell Biochem. 2020 Nov;474(1-2):285-294. doi: 10.1007/s11010-020-03852-1. Epub 2020 Aug 10.

DOI:10.1007/s11010-020-03852-1
PMID:32779043
Abstract

Alzheimer's disease (AD) is a public health issue worldwide. Berberine (Ber) acts as the neuroprotective role in an animal experiment of AD. MicroRNA-188 (miRNA-188) was reported to be decreased in primary hippocampal neurons of mice. However, the roles and molecular basis of Ber and miRNA-188 in the treatment of AD need to be further explored. In this study, 5 μM Ber treatment has little effect on cell viability. Ber treatment or miR-188 overexpression expedited proliferation and inhibited caspase-3 activity and apoptotic rate in amyloid-beta (Aβ)-treated BV2 and N2a cells. MiR-188 was downregulated, and nitric oxide synthase 1 (NOS1) was upregulated in Aβ-induced BV2 and N2a cells. NOS1 worked as the target of miR-188. NOS1 overturned miR-188-induced effects on cell viability, caspase-3 activity, and apoptotic rate in Aβ-induced BV2 and N2a cells. Ber mitigated neuronal damage in Aβ-induced BV2 and N2a cells by miR-188/NOS1 axis. These results suggested that Ber accelerated cell viability and suppressed caspase-3 activity and apoptotic rate possible by miR-188/NOS1 pathway, implying the treatment of Ber as an underlying effective drug for AD patients.

摘要

阿尔茨海默病(AD)是一个全球性的公共卫生问题。小檗碱(Ber)在 AD 的动物实验中具有神经保护作用。据报道,miRNA-188(miRNA-188)在小鼠原代海马神经元中减少。然而,Ber 和 miRNA-188 在 AD 治疗中的作用和分子基础仍需进一步探索。在本研究中,5μM Ber 处理对细胞活力几乎没有影响。Ber 处理或 miR-188 过表达可加速增殖,并抑制 Aβ处理的 BV2 和 N2a 细胞中的 caspase-3 活性和凋亡率。miR-188 在 Aβ诱导的 BV2 和 N2a 细胞中下调,一氧化氮合酶 1(NOS1)上调。NOS1 是 miR-188 的靶基因。NOS1 逆转了 miR-188 对 Aβ诱导的 BV2 和 N2a 细胞中细胞活力、caspase-3 活性和凋亡率的影响。Ber 通过 miR-188/NOS1 轴减轻 Aβ诱导的 BV2 和 N2a 细胞中的神经元损伤。这些结果表明,Ber 通过 miR-188/NOS1 通路加速细胞活力并抑制 caspase-3 活性和凋亡率,提示 Ber 作为 AD 患者的潜在有效药物。

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