Although previous studies showed that exercise can improve cognitive dysfunction in type 2 diabetes (T2DM), the underlying mechanism remains unclear. Sirtuin 1 (SIRT1) has been shown to play a role in regulating inflammatory responses in the brain and increasing BDNF expression. This study investigated the effects of treadmill exercise on the hippocampal inflammatory response and BDNF expression in a T2DM mice model. We also tested whether these effects are SIRT1-dependent. In this study, C57BL/ 6 mice were used to construct T2DM model by a high-fat diet and STZ injection. We found that treadmill exercise for 8 weeks can significantly improve the cognitive dysfunction, alleviate activation of proinflammatory microglia M1 (Iba1 labeling) in the hippocampus of T2DM mice, and reduce the levels of proinflammatory factors IL-1β, IL-6, TNF-α, increase the expression levels of anti-inflammatory factors IL-10, TGF-β1, and promote the release of BDNF. We also found that exercise activate the signaling pathway of SIRT1/ NF-κB and SIRT1/ PGC-1α/ FNDC5/ BDNF. After the application of nicotinamide (NAM, SIRT1 inhibitor), the positive effects of exercise were remarkably suppressed. Our results showed that long-term moderate intensity treadmill exercise can alleviate inflammatory response in the hippocampus and increase BDNF expression in T2DM mice by activating SIRT1.

尽管之前的研究表明运动可以改善 2 型糖尿病 (T2DM) 的认知功能障碍，但其潜在机制仍不清楚。Sirtuin 1 (SIRT1) 已被证明在调节大脑炎症反应和增加 BDNF 表达方面发挥作用。本研究调查了跑步机运动对 T2DM 小鼠模型海马炎症反应和 BDNF 表达的影响。我们还测试了这些影响是否依赖于 SIRT1。本研究采用C57BL/6小鼠通过高脂饮食和STZ注射构建T2DM模型。我们发现跑步机运动8周可以显着改善认知功能障碍，减轻T2DM小鼠海马促炎性小胶质细胞M1（Iba1标记）的激活，降低促炎因子IL-1β、IL-6、TNF-α的水平, 增加抗炎因子IL-10、TGF-β1的表达水平，促进BDNF的释放。我们还发现运动可以激活 SIRT1/NF-κB 和 SIRT1/PGC-1α/FNDC5/BDNF 的信号通路。应用烟酰胺（NAM，SIRT1抑制剂）后，运动的积极作用明显受到抑制。我们的结果表明，长期中等强度的跑步机运动可以通过激活 SIRT1 来减轻海马区的炎症反应并增加 T2DM 小鼠的 BDNF 表达。