Background: In diabetes, cognitive impairment is linked with oxidative stress and neuroinflammation. As the only chimeric member of the galectin family, galectin-3 (Gal3) induces neuroinflammation and cognitive impairment in models of Alzheimer’s disease (AD); however, its role in diabetes-associated cognitive impairment is not established.
Methodology: Here, we investigated the effects of Gal3 inhibition on cognitive impairment and the possible underlying molecular events in diabetes. We investigated the effects of the Gal3 inhibitor modified citrus pectin (MCP; 100 mg/kg/day oral for 6 weeks) in vivo in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Additionally, the effects of MCP on high glucose (HG)-stimulated BV-2 microglial cells were investigated in vitro.
Results: We found that MCP attenuated memory impairment in diabetic rats in the Morris water maze test and reduced insulin resistance, oxidative stress, and neuroinflammation. In HG-stimulated BV-2 microglial cells, MCP increased cell viability and decreased oxidative stress and the production of proinflammatory cytokines.
Conclusion: The results of this study indicate that the inhibition of Gal3 by MCP ameliorates diabetes-associated cognitive impairment, oxidative stress, and neuroinflammation, suggesting that Gal3 could be a potential new target for therapeutic intervention to prevent cognitive impairment in diabetes.



中文翻译：

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Galectin-3 的药理抑制作用可在体内和体外改善糖尿病相关的认知障碍、氧化应激和神经炎症

背景：在糖尿病中，认知障碍与氧化应激和神经炎症有关。作为半乳糖凝集素家族中唯一的嵌合成员，半乳糖凝集素 3 (Gal3) 在阿尔茨海默病 (AD) 模型中诱导神经炎症和认知障碍；然而，它在糖尿病相关认知障碍中的作用尚未确定。
方法：在这里，我们研究了 Gal3 抑制对认知障碍的影响以及糖尿病中可能的潜在分子事件。我们在高脂饮食 (HFD)/链脲佐菌素 (STZ) 诱导的糖尿病大鼠体内研究了 Gal3 抑制剂修饰的柑橘果胶 (MCP; 100 mg/kg/天口服 6 周) 在体内的影响。此外，在体外研究了 MCP 对高葡萄糖 (HG) 刺激的 BV-2 小胶质细胞的影响。
结果：我们发现 MCP 在莫里斯水迷宫试验中减轻了糖尿病大鼠的记忆障碍，并降低了胰岛素抵抗、氧化应激和神经炎症。在 HG 刺激的 BV-2 小胶质细胞中，MCP 增加了细胞活力并减少了氧化应激和促炎细胞因子的产生。
结论：本研究结果表明，MCP 抑制 Gal3 可改善糖尿病相关的认知障碍、氧化应激和神经炎症，表明 Gal3 可能成为预防糖尿病认知障碍的治疗干预的潜在新靶点。