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不同运动类型对2型糖尿病小鼠肠道机械屏障及相关调节信号的影响

孙姜楠, 侯豹, 艾敏, 于晓依, 蔡维维, 邱丽颖^*

江南大学无锡医学院基础医学系，无锡 214100

摘要

本文旨在探究不同运动类型对2型糖尿病(type 2 diabetes mellitus, T2DM)小鼠肠道机械屏障及相关调节信号的影响。通过高脂饲料喂养和腹腔注射链脲佐菌素(streptozocin, STZ)制备T2DM小鼠模型。将小鼠分为对照组、模型组(自由活动)、抗阻运动组(每周5次尾部负重爬梯运动)、有氧运动组(每周5次无负重跑台运动)和联合运动组(每周第一、三、五天进行有氧运动，第二、四天进行抗阻运动)。8周干预完成后，用ELISA试剂盒检测小鼠血清脂质水平和炎症因子，用HE和PAS染色法观察回肠病理学变化，用实时荧光定量PCR和免疫印迹分别检测肠道紧密连接相关蛋白mRNA和蛋白表达水平，并检测缺氧诱导因子1α (hypoxia inducible factor-1α, HIF-1α)和肌球蛋白轻链激酶(myosin light chain kinase, MLCK)蛋白的表达。结果显示，和模型组相比，三种运动都能降低血糖，减轻体重。有氧运动和联合运动降低血清脂质(甘油三酯和总胆固醇)水平，上调回肠组织紧密连接相关蛋白和HIF-1α的表达，提高肠道碱性磷酸酶(alkaline phosphatase, AKP)活性，降低血清脂多糖(lipopolysaccharide, LPS)、白介素-1β (interleukin-1β, IL-1β)、肿瘤坏死因子α (tumor necrosis factor-α, TNF-α)和二胺氧化酶(diamine oxidase, DAO)水平，下调回肠组织MLCK蛋白的表达水平。上述结果提示，三种运动都能降低T2DM小鼠血糖、减轻体重，有氧运动和联合运动还能恢复被破坏的肠道机械屏障，其机制可能与HIF-1α-MLCK通路有关。

关键词： 运动方式; 2型糖尿病; 肠道机械屏障

The effect of different types of exercise on the intestinal mechanical barrier and related regulatory factors in type 2 diabetic mice 

SUN Jiang-Nan, HOU Bao, AI Min, YU Xiao-Yi, CAI Wei-Wei, QIU Li-Ying^*

Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi 214100, China

Abstract

The aim of this study was to investigate the effects of different types of exercise on intestinal mechanical barrier and related regulatory factors in mice with type 2 diabetes mellitus (T2DM). The model was established by high-fat diet feeding and intraperitoneal injection of streptozocin (STZ). The mice were divided into control group, model group (free exercise), resistance exercise group (tail load-bearing ladder climbing, 5 times a week), aerobic exercise group (non-load-bearing platform running, 5 times a week at a speed of 10–15 m/min), and combined exercise group (aerobic exercise was performed on the first, third and fifth days of each week, and resistance exercise on the second and fourth days of each week). After 8 weeks of intervention, the serum lipid levels and inflammatory cytokines were measured by corresponding kits. The pathological changes of ileum were detected by HE and PAS staining. The mRNA and protein expression levels of tight junction-related proteins were detected by real-time qPCR and Western blot, respectively. Moreover, the protein expression levels of hypoxia inducible factor-1α (HIF-1α) and myosin light chain kinase (MLCK) were detected by Western blot. The results showed that all three types of exercise decreased blood glucose and body weight compared to the model group. Aerobic exercise and combined exercise decreased serum lipid (triglycerides and total cholesterol) levels, up-regulated the expression levels of ileal tight junction-related proteins and HIF-1α, improved the intestinal alkaline phosphatase (AKP) activity, reduced serum lipopolysaccharide (LPS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and diamine oxidase (DAO) levels, and down-regulated MLCK protein expression level. These results suggest that all three types of exercise can reduce blood glucose and body weight of T2DM mice, and aerobic exercise and combined exercise can restore the damaged intestinal mechanical barrier by a mechanism involving HIF-1α-MLCK pathway.

Key words: exercise types; type 2 diabetes; intestinal mechanical barrier

收稿日期：　　录用日期：

通讯作者：邱丽颖　　E-mail: qiulydoc@sina.com

DOI: 10.13294/j.aps.2022.0030

引用本文：

孙姜楠, 侯豹, 艾敏, 于晓依, 蔡维维, 邱丽颖. 不同运动类型对2型糖尿病小鼠肠道机械屏障及相关调节信号的影响[J]. 生理学报 2022; 74 (2): 237-245.

SUN Jiang-Nan, HOU Bao, AI Min, YU Xiao-Yi, CAI Wei-Wei, QIU Li-Ying. The effect of different types of exercise on the intestinal mechanical barrier and related regulatory factors in type 2 diabetic mice . Acta Physiol Sin 2022; 74 (2): 237-245 (in Chinese with English abstract).