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有氧运动降低胰岛素抵抗小鼠海马细胞焦亡相关蛋白及炎症因子的表达

卞学鹏¹, 姬瑞方¹, 刘蓓蓓^1,2, 胡静芸¹, 李明明¹, 薛香莉¹, 娄淑杰^1,*

¹上海体育学院运动科学学院，上海 200438；²潍坊医学院康复医学院，潍坊 261053

摘要

本研究通过观察高脂饮食及有氧运动干预后小鼠海马细胞焦亡及炎症相关蛋白的表达情况，探讨运动改善胰岛素抵抗(insulin resistance, IR)的可能机制。选取6周龄C57BL/6J雄性小鼠38只，随机以正常饮食(n = 12)或高脂饮食(n = 26)喂养12周后进行葡萄糖和胰岛素耐量实验，根据结果将小鼠分为对照组(n = 12)、IR组(n = 10)和IR有氧运动组(n = 10)。IR有氧运动组进行12周的渐增跑台训练。干预结束后麻醉处死小鼠并剥离海马组织，提取蛋白进行Western blot实验，检测细胞焦亡及炎症相关蛋白的表达情况。结果显示：(1)与对照组相比，IR小鼠海马NFκB，炎症小体相关蛋白 Nod样受体蛋白3 (Nod-likereceptor protein 3, NLRP3)、斑点样蛋白(apoptosis-associated speck-like protein containing CARD, ASC)，细胞焦亡相关蛋白pro-Caspase-1、gasdermin D (GSDMD)、GSDMD-N及炎症因子IL-1β、IL-18均显著升高，而炎症小体相关蛋白NIMA相关蛋白激酶7 (NIMA-related kinase 7, NEK7)及焦亡相关蛋白 Caspase-1有升高趋势，但无显著差异。(2)与IR组相比，渐增跑台训练能够显著降低IR小鼠海马NFκB、NLRP3、NEK7、ASC、pro-Caspase-1、GSDMD、GSDMD-N、IL-1β、IL-18的表达。以上结果提示，12周渐增跑台训练能够显著降低IR小鼠海马焦亡相关蛋白及炎症因子表达，抑制细胞焦亡。

关键词： 细胞焦亡; 胰岛素抵抗; 有氧运动; NLRP3炎症小体; GSDMD

分类号：R339.4; R34; R493

Aerobic exercise reduces the expression of pyroptosis-related proteins and inflammatory factors in hippocampus of mice with insulin resistance

BIAN Xue-Peng¹, JI Rui-Fang¹, LIU Bei-Bei^1,2, HU Jing-Yun¹, LI Ming-Ming¹, XUE Xiang-Li¹, LOU Shu-Jie^1,*

¹School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China；²School of Rehabilitation Medicine, Weifang Medical University, Weifang 261053, China

Abstract

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1β, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.

Key words: pyroptosis; insulin resistance; aerobic exercise; NLRP3 inflammasome; GSDMD

收稿日期：2019-07-23　　录用日期：2019-09-24

通讯作者：娄淑杰　　E-mail: shujielou319@163.com

DOI: 10.13294/j.aps.2020.0002

引用本文：

卞学鹏, 姬瑞方, 刘蓓蓓, 胡静芸, 李明明, 薛香莉, 娄淑杰. 有氧运动降低胰岛素抵抗小鼠海马细胞焦亡相关蛋白及炎症因子的表达[J]. 生理学报 2020; 72 (4): 455-462.

BIAN Xue-Peng, JI Rui-Fang, LIU Bei-Bei, HU Jing-Yun, LI Ming-Ming, XUE Xiang-Li, LOU Shu-Jie. Aerobic exercise reduces the expression of pyroptosis-related proteins and inflammatory factors in hippocampus of mice with insulin resistance. Acta Physiol Sin 2020; 72 (4): 455-462 (in Chinese with English abstract).