Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China.
Department of Pediatrics, Tianjin Children's Hospital, Beichen, Tianjin, P.R. China.
Aging (Albany NY). 2021 Mar 26;13(7):10659-10671. doi: 10.18632/aging.202830.
The mechanisms underlying the development of neuropathy associated with diabetes mellitus are not fully understood. Resveratrol, as a nonflavonoid polyphenol, plays a variety of beneficial roles in the treatment of chronic diseases such as Alzheimer's disease, coronary heart disease and obesity. In our study, the role of nuclear erythroid 2-related factor 2 (Nrf2) in resveratrol-mediated protection against streptozotocin-induced diabetic peripheral neuropathy (DPN) was investigated, and the antioxidant effect of resveratrol in diabetic peripheral nerves was studied. The STZ-treated model mice were divided into two groups. The resveratrol group was intragastrically administered 10 ml/kg 10% resveratrol once a day until the 12th week after STZ injection. The vehicle-treated mice were injected with the same volume of DMSO. Analysis of the effects of resveratrol in DPN revealed the following novel findings: (i) the pain and temperature sensitivities of diabetic mice were improved after treatment with resveratrol; (ii) Nrf2 expression was increased in the diabetic peripheral nerves of resveratrol-treated mice, and NF-KB pathway inhibition protected nerves upon resveratrol treatment in peripheral neuropathy; and (iii) resveratrol modulated the anti-inflammatory microenvironment of peripheral nerves by increasing Nrf2 activation and the expression of p-p65, and these changes may have been responsible for the neuroprotective effect of resveratrol in DPN, which was confirmed by Nrf2 knockout in diabetic mice. Overall, this study demonstrates that resveratrol may attenuate the severity of DPN by protecting peripheral nerves from apoptosis by inhibiting the NF-KB pathway and increasing Nrf2 expression.
糖尿病相关神经病变的发病机制尚未完全阐明。白藜芦醇作为一种非黄酮多酚，在治疗阿尔茨海默病、冠心病和肥胖症等慢性疾病方面发挥着多种有益作用。在我们的研究中，研究了核红细胞 2 相关因子 2 (Nrf2) 在白藜芦醇介导的防治链脲佐菌素诱导的糖尿病周围神经病变 (DPN) 中的作用，并研究了白藜芦醇在糖尿病周围神经中的抗氧化作用。将 STZ 处理的模型小鼠分为两组。白藜芦醇组每天灌胃 10%白藜芦醇 10ml/kg，直至 STZ 注射后 12 周。用相同体积的 DMSO 处理载体处理的小鼠。分析白藜芦醇在 DPN 中的作用发现了以下新发现：（i）白藜芦醇治疗后糖尿病小鼠的疼痛和温度敏感性得到改善；（ii）白藜芦醇处理的糖尿病小鼠周围神经中 Nrf2 表达增加，NF-KB 通路抑制可保护神经在周围神经病变中白藜芦醇治疗时；（iii）白藜芦醇通过增加 Nrf2 激活和 p-p65 的表达来调节周围神经的抗炎微环境，这些变化可能是白藜芦醇在 DPN 中具有神经保护作用的原因，这在糖尿病小鼠的 Nrf2 敲除中得到了证实。总的来说，这项研究表明，白藜芦醇可能通过抑制 NF-KB 通路和增加 Nrf2 表达来保护外周神经免受凋亡，从而减轻 DPN 的严重程度。
