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灯盏花乙素通过 JAK2/STAT3 信号通路对 BV-2 小胶质细胞介导的 PC12 细胞凋亡的影响。

Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.

机构信息

Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, China.

出版信息

Sci Rep. 2024 Jun 11;14(1):13430. doi: 10.1038/s41598-024-64226-x.

Abstract

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

摘要

先前的研究表明,野黄芩苷可抑制小胶质细胞过度激活,减少神经元凋亡,发挥神经保护作用。然而,野黄芩苷是否通过 JAK2/STAT3 信号通路调节激活的小胶质细胞介导的神经元凋亡及其机制尚不清楚。本研究旨在探讨野黄芩苷是否可以通过 JAK2/STAT3 信号通路减轻激活的小胶质细胞诱导的 PC12 细胞凋亡。用氧葡萄糖剥夺(OGD)培养基培养小胶质细胞作为条件培养基(CM)来激活 PC12 细胞,以研究凋亡和 JAK2/STAT3 信号相关蛋白的表达。我们观察到 CM 中 PC12 细胞凋亡明显增加,促凋亡蛋白 Bax 和凋亡相关蛋白 cleaved caspase-3 的表达和荧光强度增加,抗凋亡蛋白 B 细胞淋巴瘤-2(Bcl-2)的表达减少。JAK2/STAT3 信号通路相关蛋白 JAK2 和 STAT3 的磷酸化水平和荧光强度降低。用野黄芩苷处理后,PC12 细胞凋亡以及 cleaved caspase-3 和 Bax 蛋白的表达和荧光强度降低。Bcl-2、磷酸化 JAK2 和 STAT3 的表达和荧光强度增加。使用 JAK2/STAT3 信号通路的特异性抑制剂 AG490。我们的研究结果表明,AG490 可减弱野黄芩苷的作用。我们的研究表明,野黄芩苷抑制 OGD 激活的小胶质细胞介导的 PC12 细胞凋亡,这是通过 JAK2/STAT3 信号通路调节的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112f/11166921/acc15a3dc353/41598_2024_64226_Fig1_HTML.jpg

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