Background Glucose fluctuation promotes neuronal apoptosis, which plays a central role in diabetic encephalopathy (DE). Nerve growth factor (NGF), and its interaction with high-affinity (TrkA) and low-affinity (p75NTR) receptors, are involved in neuronal survival. NGF/TrkA contributes to the activation of the PI3K/AKT pathway, which is beneficial for neuronal survival, and α-Lipoic acid (ALA) exerts clinically favorable neuroprotective effects in the periphery. Whether NGF receptors and the PI3K/AKT pathway are involved in glucose fluctuation-induced neuronal damage, as well as the potential molecular mechanism of ALA in protecting glucose fluctuation-induced neuronal damage, remain unclear. Results The results indicated that constant high glucose (CHG) and intermittent high glucose (IHG) significantly increased the expression of Bax and caspase-3, and decreased the expression of TrkA/p75NTR and p-AKT/AKT, while ALA stimulation reversed the above proteins in PC12 cells. IHG stimulates apoptosis more effectively than CHG in PC12 cells, which is related to the PI3K/AKT pathway but not to the TrkA/p75NTR. Furthermore, neuronal apoptosis induced by IHG was aggravated by the TrkA inhibitor K252a or the PI3K/AKT inhibitor LY294002, but this effect was alleviated by the p75NTR inhibitor TAT-pep5. Conclusion Glucose fluctuation induced cell apoptosis by regulating the TrkA/p75NTR and PI3K/AKT pathway, meanwhile ALA exhibited neuroprotective effects in response to IHG and CHG. These observations indicated that the PI3K/AKT pathway and the balance of TrkA/p75NTR are likely to serve as potential therapeutic targets for DE. In addition, ALA could be a possible therapeutic drug for DE.

中文翻译：

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NGF受体和PI3K/AKT通路参与葡萄糖波动诱导的神经元损伤和α-硫辛酸治疗

背景葡萄糖波动促进神经元凋亡，这在糖尿病脑病 (DE) 中起核心作用。神经生长因子 (NGF) 及其与高亲和力 (TrkA) 和低亲和力 (p75NTR) 受体的相互作用与神经元存活有关。NGF/TrkA 有助于激活 PI3K/AKT 通路，这有利于神经元存活，α-硫辛酸 (ALA) 在外周发挥临床上有利的神经保护作用。NGF受体和PI3K/AKT通路是否参与葡萄糖波动诱导的神经元损伤，以及ALA保护葡萄糖波动诱导的神经元损伤的潜在分子机制尚不清楚。结果 结果表明，持续高糖（CHG）和间歇性高糖（IHG）显着增加Bax和caspase-3的表达，并降低 TrkA/p75NTR 和 p-AKT/AKT 的表达，而 ALA 刺激逆转了 PC12 细胞中的上述蛋白质。IHG 在 PC12 细胞中比 CHG 更有效地刺激细胞凋亡，这与 PI3K/AKT 通路有关，但与 TrkA/p75NTR 无关。此外，TrkA 抑制剂 K252a 或 PI3K/AKT 抑制剂 LY294002 会加剧 IHG 诱导的神经元凋亡，但 p75NTR 抑制剂 TAT-pep5 可减轻这种影响。结论 葡萄糖波动通过调节TrkA/p75NTR和PI3K/AKT通路诱导细胞凋亡，同时ALA对IHG和CHG具有神经保护作用。这些观察结果表明 PI3K/AKT 通路和 TrkA/p75NTR 的平衡可能作为 DE 的潜在治疗靶点。此外，ALA 可能是 DE 的一种可能的治疗药物。