抗阻运动对胰岛素抵抗小鼠海马内焦亡相关蛋白的影响*

doi:10.12047/j.cjap.5969.2020.097

摘要/Abstract

摘要： 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。

关键词: 抗阻运动, 胰岛素抵抗, 海马, NLRP3炎症小体, 焦亡, 小鼠

Abstract: 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.

Key words: resistance training, insulin resistance, hippocampus, NLRP3 inflammasome, mice

中图分类号:

G804.2

姬瑞方, 卞学鹏, 刘蓓蓓, 胡静芸, 薛香莉, 娄淑杰. 抗阻运动对胰岛素抵抗小鼠海马内焦亡相关蛋白的影响^*[J]. 中国应用生理学杂志, 2020, 36(5): 456-461.

JI Rui-fang, BIAN Xue-peng, LIU Bei-bei, HU Jing-yun, XUE Xiang-li, LOU Shu-jie. Effects of resistance exercise on pyroptosis-related proteins in hippocampus of insulin resistant mice[J]. CJAP, 2020, 36(5): 456-461.

参考文献

[1] Riccardi G, Giacco R, Rivellese AA. Dietary fat, insulin sensitivity and the metabolic syndrome[J]. Clin Nutr, 2004, 23(4): 447-456.
[2] Kim B, Feldman EL. Insulin resistance in the nervous system[J]. Trends Endocrinol Metab, 2012, 23(3): 133-141.
[3] Onyango AN. Cellular stresses and stress responses in the pathogenesis of insulin resistance[J]. Oxid Med Cell Longev, 2018, 2018: 4321714.
[4] He WT, Wan H, Hu L, et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion[J]. Cell Res, 2015, 25(12): 1285-1298.
[5] Sharma A, Tate M, Mathew G, et al. Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: Therapeutic implications[J]. Front Physiol, 2018, 9: 114.
[6] Vande Walle L, Lamkanfi M. Pyroptosis[J]. Curr Biol, 2016, 26(13): R568-R572.
[7] 高文青. Pyrin炎症小体激活的分子机制与Gasdermin E介导的细胞焦亡的研究[D]. 中国农业大学, 2017.
[8] Li J, Liu Y, Liu B, et al. Mechanisms of aerobic exercise upregulating the expression of hippocampal synaptic plasticity-associated proteins in diabetic rats[J]. Neural Plast, 2019, 2019: 7920540.
[9] Ruderman NB, Xu XJ, Nelson L, et al. AMPK and SIRT1: a long-standing partnership[J]? Am J Physiol Endocrinol Metab, 2010, 298(4): E751-760.
[10]Haneklaus M, O'neill LA. NLRP3 at the interface of metabolism and inflammation[J]. Immunol Rev, 2015, 265(1): 53-62.
[11]Sun X, Hao H, Han Q, et al. Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance by suppressing NLRP3 inflammasome-mediated inflammation in type 2 diabetes rats[J]. Stem Cell Res Ther, 2017, 8(1): 241.
[12]Dai X, Okon I, Liu Z, et al. Ablation of neuropilin 1 in myeloid cells exacerbates high-fat diet-induced insulin resistance through Nlrp3 inflammasome in vivo[J]. Diabetes, 2017, 66(9): 2424-2435.
[13]Zhao RR, O'sullivan AJ, Fiatarone Singh MA. Exercise or physical activity and cognitive function in adults with type 2 diabetes, insulin resistance or impaired glucose tolerance: a systematic review[J]. Eur Rev Aging Phys Act, 2018, 15: 1.
[14]Pesta DH, Goncalves RLS, Madiraju AK, et al. Resistance training to improve type 2 diabetes: working toward a prescription for the future[J]. Nutr Metab (Lond), 2017, 14: 24.
[15]Leite RD, Durigan Rde C, De Souza Lino AD, et al. Resistance training may concomitantly benefit body composition, blood pressure and muscle MMP-2 activity on the left ventricle of high-fat fed diet rats[J]. Metabolism, 2013, 62(10): 1477-1484.
[16]Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level[J]. Nat Rev Mol Cell Biol, 2008, 9(3): 231-241.
[17]Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death[J]. Nature, 2015, 526(7575): 660-665.
[18]Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family[J]. Nature, 2016, 535(7610): 111.
[19]Zhai Y, Meng X, Ye T, et al. Inhibiting the NLRP3 inflammasome activation with MCC950 ameliorates diabetic encephalopathy in db/db mice[J]. Molecules, 2018, 23: 1-14.
[20]李静静. 基于代谢组学探究运动上调糖尿病大鼠海马突触可塑相关蛋白表达的可能机制[D]. 上海体育学院, 2018.
[21]Ruderman NB, Carling D, Prentki M, et al. AMPK, insulin resistance, and the metabolic syndrome[J]. J Clin Invest, 2013, 123(7): 2764-2772.
[22]Lin CF, Kuo YT, Chen TY, et al. Quercetin-rich guava (Psidium guajava) juice in combination with trehalose reduces autophagy, apoptosis and pyroptosis formation in the kidney and pancreas of type II diabetic rats[J]. Molecules, 2016, 21(3): 334.
[23]Fan Y, Du L, Fu Q, et al. Inhibiting the NLRP3 inflammasome With MCC950 ameliorates isoflurane-induced pyroptosis and cognitive impairment in aged mice[J]. Front Cell Neurosci, 2018, 12: 426.

抗阻运动对胰岛素抵抗小鼠海马内焦亡相关蛋白的影响^*

Effects of resistance exercise on pyroptosis-related proteins in hippocampus of insulin resistant mice

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