Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Phytother Res. 2021 Aug;35(8):4592-4604. doi: 10.1002/ptr.7177. Epub 2021 Jun 4.
Oxidative stress plays the main role in the pathogenesis of diabetes mellitus and peripheral neuropathy. Polydatin (PD) has been shown to exhibit strong antioxidative and antiinflammatory effects. At present, no research has focused on the possible effects of PD on Schwann cells and impaired peripheral nerves in diabetic models. Here, we used an in vitro Schwann cell damage model induced by methylglyoxal and an in vivo diabetic sciatic nerve crush model to study problems in such an area. In our experiment, we demonstrated that PD potently alleviated the decrease of cellular viability, prevented reactive oxygen species generation, and suppressed mitochondrial depolarization as well as cellular apoptosis in damaged Schwann cells. Moreover, we found that PD could upregulate Nrf2 and Glyoxalase 1 (GLO1) expression and inhibit Keap1 and receptor of AGEs (RAGE) expression of damaged Schwann cells. Finally, our in vivo experiment showed that PD could promote sciatic nerves repair of diabetic rats. Our results revealed that PD exhibited prominent neuroprotective effects on Schwann cells and sciatic nerves in diabetic models. The molecular mechanisms were associated with activating Nfr2 and GLO1 and inhibiting Keap1 and RAGE.
氧化应激在糖尿病及其外周神经病变的发病机制中起主要作用。虎杖苷（PD）已被证明具有很强的抗氧化和抗炎作用。目前，尚无研究关注 PD 对糖尿病模型中施万细胞和受损周围神经的可能影响。在这里，我们使用甲基乙二醛诱导的体外施万细胞损伤模型和体内糖尿病坐骨神经挤压模型来研究这方面的问题。在我们的实验中，我们证明 PD 能够有效缓解受损施万细胞活力下降、抑制活性氧生成和线粒体去极化以及细胞凋亡。此外，我们发现 PD 可以上调 Nrf2 和 Glyoxalase 1（GLO1）的表达，并抑制受损施万细胞中 Keap1 和晚期糖基化终产物受体（RAGE）的表达。最后，我们的体内实验表明 PD 可以促进糖尿病大鼠坐骨神经的修复。我们的结果表明，PD 对糖尿病模型中的施万细胞和坐骨神经具有显著的神经保护作用。其分子机制与激活 Nfr2 和 GLO1 以及抑制 Keap1 和 RAGE 有关。
