雷公藤内酯醇通过抑制TLR4/NF-κB通路减轻皮质神经元缺氧/复氧损伤

doi:10.3969/j.issn.1006-6233.2024.05.010

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Abstract Objective: To investigate the effects of Triptolide (TPL) on hypoxia/reoxygenation (H/R) injury of cortical neurons and explore its mechanism based on toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway. Methods: The cortical neurons of SD suckling rats were isolated and cultured in vitro, and the H/R damaged cortical neuron model was prepared by hypoxia for 4h and then reoxygenation for 24h. The normal control group, model group, TPL (25mg/L) group, TPL (25mg/L) +TAK242 (TLR4 inhibitor, 1mg/L) group, TPL (25mg/L)+LPS (TLR4 agonist, 0.1mg/L) group were set up. 24h after administrating separately, the neuronal activity was detected by MTT, the neuronal apoptosis was detected by flow cytometry. The content of inflammatory factors (TNF-α, IL-1β, IL-6) were detected by ELISA. The TLR4/NF-κB signaling pathway related proteins [TLR4, NF-κB p65, p-NF-κB p65, B-lymphoblastoma-2 gene (bcl-2), bcl-2 associated X protein (Bax), Caspase-3, cleaved Caspase-3] were detected by Western blot. Results: Compared with the model group, the activity of cortical neuron in TPL group was increased while the apoptosis rate was decreased (P<0.05). The content of TNF-α, IL-1β, IL-6 in culture medium were significantly decreased (P<0.05). The expression of TLR4 and the expression ratio of p-NF-κB p65/NF-κB p65, Bax/bcl-2, cleaved Caspase-3/Caspase-3 were significantly decreased (P<0.05). TAK242 could significantly enhance the regulatory effects of TPL on the activity, apoptosis, inflammatory factors content and the expression of TLR4/NF-κB signaling pathway related protein in H/R damaged cortical neurons. And LPS could significantly reversed the regulatory effects of TPL on H/R damaged cortical neurons. Conclusion: TPL can reduce inflammation and apoptosis by inhibiting the activation of TLR4/NF-κB pathway, and thus play a protective role in H/R injury of cortical neurons.

Key words： Triptolide Hypoxia/reoxygenation Cortical neurons TLR4/NF-κB pathway

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.05.010 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I5/756

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