Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou City, 121000, China.
Department of Orthopedic, Maanshan People's Hospital, Ma'anshan City, China.
Can J Physiol Pharmacol. 2021 Aug;99(8):768-774. doi: 10.1139/cjpp-2020-0373. Epub 2020 Nov 17.
Metformin, the first medication that is often prescribed for the treatment of type 2 diabetes mellitus, was recently found to be neuroprotective. To study the mechanism underlying the neuroprotective effect of metformin, we pretreated primary spinal cord neurons with 50 µM or 100 µM metformin for 2 h prior to treatment with hydrogen peroxide (HO) for up to 48 h. Our results showed that HO increased the expression of purinergic receptor P2X7 (P2X7R) in spinal cord neurons, which promoted the downstream pro-inflammatory cytokines release and oxidative stress. We found that metformin could reverse these pro-inflammatory and pro-oxidative effects of HO. Besides, P2X7R knockdown by siRNA suppressed HO-induced pro-inflammatory cytokine release and oxidative stress response. In conclusion, our results show that metformin can alleviate HO-induced inflammation and oxidative stress via modulating the P2X7R signaling pathway.
二甲双胍是治疗 2 型糖尿病常用的第一种药物，最近发现其具有神经保护作用。为了研究二甲双胍的神经保护作用机制，我们先用 50µM 或 100µM 的二甲双胍预处理原代脊髓神经元 2 小时，然后再用过氧化氢（HO）处理 48 小时。结果显示，HO 增加了脊髓神经元嘌呤能受体 P2X7（P2X7R）的表达，从而促进下游促炎细胞因子的释放和氧化应激。我们发现，二甲双胍可以逆转 HO 的这些促炎和促氧化作用。此外，siRNA 敲低 P2X7R 可抑制 HO 诱导的促炎细胞因子释放和氧化应激反应。总之，我们的结果表明，二甲双胍可以通过调节 P2X7R 信号通路减轻 HO 诱导的炎症和氧化应激。
