Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China; Key Laboratory of Efficacy Evaluation of Traditional Chinese Medicine and Encephalopathy Research of Zhejiang Province, Wenzhou, 325035, China.
Innocation Academy of Testing Technology, Wenzhou Medical University, China.
Neuropharmacology. 2024 Oct 1;257:110049. doi: 10.1016/j.neuropharm.2024.110049. Epub 2024 Jun 18.
Type 2 diabetes (T2D), a chronic metabolic disease, occurs brain dysfunction accompanied with neuroinflammation and metabolic disorders. The neuroprotective effects of the basic fibroblast growth factor (bFGF) have been well studied. However, the mechanism underlying the anti-inflammatory effects of bFGF remains elusive.
In this study, db/db mice were employed as an in vivo model, while high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells were used as in vitro models. Liposomal transfection of MyD88 DNA plasmid was used for MyD88-NF-κB pathway studies. And western blotting, flow cytometry and qPCR were employed. H-NMR metabolomics was used to find out metabolic changes.
bFGF mitigated neuroinflammatory and metabolic disorders by inhibiting cortical inflammatory factor secretion and microglia hyperactivation in the cortex of db/db mice. Also, bFGF was observed to inhibit the MyD88-NF-κB pathway in high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells in in vitro experiments. Moreover, the H-NMR metabolomics results showed that discernible disparities between the cortical metabolic profiles of bFGF-treated db/db mice and their untreated counterparts. Notably, excessive lactate and choline deficiency attenuated the anti-inflammatory protective effect of bFGF in SY5Y cells.
bFGF ameliorates neuroinflammation in db/db mice by inhibiting the MyD88-NF-kB pathway. This finding expands the potential application of bFGF in the treatment of neuroinflammation-related cognitive dysfunction.
2 型糖尿病（T2D）是一种慢性代谢性疾病，发生脑功能障碍伴神经炎症和代谢紊乱。碱性成纤维细胞生长因子（bFGF）的神经保护作用已得到充分研究。然而，bFGF 抗炎作用的机制仍不清楚。
本研究采用 db/db 小鼠作为体内模型，高糖（HG）诱导的 SY5Y 细胞和 LPS 诱导的 BV2 细胞作为体外模型。采用 MyD88 DNA 质粒脂质体转染研究 MyD88-NF-κB 通路。采用 Western blot、流式细胞术和 qPCR 进行检测。采用 H-NMR 代谢组学寻找代谢变化。
bFGF 通过抑制 db/db 小鼠皮质炎症因子分泌和皮质小胶质细胞过度激活来减轻神经炎症和代谢紊乱。此外，在体外实验中，bFGF 被观察到抑制高糖（HG）诱导的 SY5Y 细胞和 LPS 诱导的 BV2 细胞中的 MyD88-NF-κB 通路。此外，H-NMR 代谢组学结果显示，bFGF 处理的 db/db 小鼠皮质代谢图谱与未处理组之间存在明显差异。值得注意的是，过量的乳酸和胆碱缺乏会削弱 bFGF 在 SY5Y 细胞中的抗炎保护作用。
bFGF 通过抑制 MyD88-NF-kB 通路改善 db/db 小鼠的神经炎症。这一发现扩展了 bFGF 在治疗神经炎症相关认知功能障碍方面的潜在应用。
