Objective: To investigate the changes of pyroptosis-related proteins in the hippocampus of insulin-resistant mice and the regulation of resistance training on pyroptosis-related proteins. Methods: Six-week-old male C57BL/6J mice were randomly divided into control group (C, n=12) and high-fat diet group (HFD, n=26) for normal or high-fat diet for 12 weeks. Subsequently, according to the results of glucose tolerance test (GTT) and insulin tolerance test (ITT), the rats fed with high-fat diet were divided into insulin resistance group (IR, n=10) and resistance exercise group (RT, n=10) as well as to maintain high-fat diet. At the same time, mice in the RT group were subjected to resistance training. After 12 weeks, all mice were sacrificed after anesthesia, brain was removed and hippocampus was exfoliated, and the expressions of pyroptosis-related proteins were detected by Western blot. Results: Compared with the C group, NF-κB, the NLRP3 inflammasome proteins, their downstream pyroptosis-related proteins GSDMD-N and GSDMD as well as inflammation factors IL-1β and IL-18 in hippocampus of IR group were significantly increased (P＜0.05), and the expression levels of SIRT1 and p-AMPK protein were significantly decreased (P＜0.05). Compared with the IR group, NF-κB, the NLRP3 inflammasome proteins, their downstream pyroptosis-related proteins GSDMD-N and GSDMD as well as inflammation factors IL-1β and IL-18 in hippocampus of RT group were significantly decreased (P＜0.05), and the expression levels of SIRT1 and p-AMPK protein were significantly increased (P＜0.01). Conclusion: NLRP3 inflammasome in the hippocampus of insulin-resistant mice is activated, which mediates pyroptosis in the hippocampus. Twelve weeks of resistance training can effectively inhibit the activation of NLRP3 inflammasome and decrease pyroptosis and improve inflammation in the hippocampus.
目的: 探讨胰岛素抵抗小鼠海马内焦亡相关蛋白的变化,以及抗阻训练对海马内焦亡相关蛋白的调节作用。方法: 6周龄C57BL/6J雄性小鼠随机分为对照组(C, n=12)和高脂膳食组(HFD, n=26)分别进行普通膳食或高脂膳食喂养12周。随后根据葡萄糖耐量实验(GTT)和胰岛素耐量实验(ITT)的结果,将HFD组分为胰岛素抵抗组(IR, n=10)和抗阻运动组(RT, n=10),维持高脂膳食喂养同时RT组小鼠进行抗阻训练。12周后,全部小鼠麻醉后处死,取脑并剥离出海马组织,通过Western blot检测焦亡相关蛋白的表达。结果: 与C组相比,IR组小鼠海马内NF-κB、NLRP3炎症小体、下游焦亡相关蛋白GSDMD-N和GSDMD以及炎症因子IL-1β和IL-18的蛋白表达量显著性上升(P＜0.05),SIRT1蛋白表达量以及p-AMPK蛋白水平显著性下降(P＜0.05);与IR组相比,RT组小鼠海马内NF-κB、NLRP3炎症小体、下游焦亡相关蛋白GSDMD-N和GSDMD以及炎症因子IL-1β和IL-18的蛋白表达量显著性下降(P＜0.05),SIRT1蛋白表达量以及p-AMPK蛋白水平显著性上升(P＜0.01)。结论: 胰岛素抵抗小鼠海马内NLRP3炎症小体被激活,介导海马内发生细胞焦亡;经过12周的抗阻运动可有效抑制NLRP3炎症小体激活,改善海马内细胞焦亡和炎症状态。.
Keywords: NLRP3 inflammasome; hippocampus; insulin resistance; mice; resistance training.