Effects of different exercise interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats

doi:10.12307/2025.274

Abstract

Abstract: BACKGROUND: Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis. However, the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed.
OBJECTIVE: To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats.
METHODS: Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group (n=12) and modeling group (n=20) after 1 week of adaptive feeding. Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin. After successful modeling, the rats were randomly divided into diabetic control group (n=6), moderate-intensity exercise group (n=6) and high-intensity intermittent exercise group (n=6). The latter two groups were subjected to treadmill training at corresponding intensities, once a day, 50 minutes each, and 5 days per week. Exercise intervention in each group was carried out for 6 weeks. After the intervention, ELISA was used to detect blood glucose and blood lipids of rats. The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining. The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR. The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence.
RESULTS AND CONCLUSION: Compared with the normal control group, fasting blood glucose, triglyceride, low-density lipoprotein cholesterol, insulin resistance index in the diabetic control group were significantly increased (P < 0.01), insulin activity was decreased (P < 0.05), and the mRNA and protein levels of carboxylesterase 1, never in mitosis gene A related kinase 7 (NEK7) and interleukin 18 in skeletal muscle tissue were upregulated (P < 0.05). Compared with the diabetic control group, fasting blood glucose, triglyceride, low-density lipoprotein cholesterol, and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated (P < 0.05), and insulin activity was increased (P < 0.05). Moreover, compared with the diabetic control group, the mRNA level of NEK7 and the protein levels of carboxylesterase 1, NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group (P < 0.05), while the mRNA levels of carboxylesterase 1, NEK7, NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group (P < 0.05). Hematoxylin-eosin staining showed that compared with the diabetic control group, the cavities of myofibers in the moderate-intensity exercise group became smaller, the number of internal cavities was reduced, and the cellular structure tended to be more intact; the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged, with irregular tissue shape and increased cavities in myofibers. To conclude, both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose, lipid, insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats. Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle, while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle. In addition, the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

Key words: moderate-intensity aerobic exercise, high-intensity intermittent exercise, type 2 diabetes, carboxylesterase 1, inflammatory factor

CLC Number:

Hu Shujuan, Cheng Ping, Zhang Xiao, Ding Yiting, Liu Xuan, Pu Rui, Wang Xianwang. Effects of different exercise interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(2): 269-278.

Figures/Tables 8

2.1 实验动物数量分析正常对照组大鼠6只与造模成功的18只大鼠全部进入结果分析。 2.2 各组大鼠体质量的变化如图1A所示，正常对照组和造模组于初始体质量比较差异无显著性意义(P > 0.05)，从第2周开始喂养高脂饲料，结果显示第2-5周造模组和正常对照组大鼠体质量变化不太明显(P > 0.05)，这可能与高脂饲料的脂肪含量不高有关；从第7周开始，与正常对照组相比，造模组大鼠体质量增加 (P < 0.05或P < 0.01)；第8周开始注射链脲佐菌素，造模组大鼠体质量增加变缓，虽高于正常对照组但差异无显著性意义(P > 0.05)。如图1B显示，运动干预前，正常对照组、中等强度运动组和高强度间歇运动组大鼠体质量略高于糖尿病对照组，但差异无显著性意义(P > 0.05)；适应性运动1周后，第2周开始正式运动干预，从运动干预第4周开始，糖尿病对照组大鼠的体质量明显低于正常对照组(P < 0.05或 P < 0.01)；从运动干预第5周开始，中等强度运动组大鼠的体质量低于正常对照组(P < 0.05或P < 0.01)；从运动干预第7周开始，高强度间歇运动组大鼠的体质量低于正常对照组(P < 0.05或P < 0.01)；中等强度运动组和高强度间歇运动组运动干预第7，8周的体质量相对于糖尿病对照组降低趋势明显，但差异无显著性意义(P > 0.05)，提示长期运动可能对降低2型糖尿病大鼠体质量有一定的效果，但运动干预6周时间未发现显著变化。 2.3 运动干预后各组大鼠空腹血糖变化如图2显示，糖尿病对照组、中等强度运动组和高强度间歇运动组大鼠空腹血糖水平始终高于正常对照组(P < 0.01)，从运动干预后的第3周开始，中等强度运动组和高强度间歇运动组大鼠空腹血糖水平明显低于糖尿病对照组(P < 0.01)，提示运动可以降低2型糖尿病大鼠空腹血糖水平；中等强度运动组和高强度间歇运动组相比，高强度间歇运动组大鼠空腹血糖水平降低趋势更明显，但差异无显著性意义 (P > 0.05)。 2.4 运动干预后各组大鼠脂代谢及胰岛素抵抗情况比较见图3。与正常对照组比较，糖尿病对照组大鼠血清三酰甘油、低密度脂蛋白胆固醇水平与胰岛素抵抗指数均升高 (P < 0.01)，胰岛素活性降低(P < 0.01)，总胆固醇、高密度脂蛋白胆固醇水平无明显变化(P > 0.05)。 6周运动干预后，与糖尿病对照组相比，中等强度运动组和高强度间歇运动组大鼠血清总胆固醇、高密度脂蛋白胆固醇水平无明显变化(P > 0.05)，中等强度运动组和高强度间歇运动组大鼠血清三酰甘油、低密度脂蛋白胆固醇水平降低(P < 0.01)，中等强度运动组和高强度间歇运动组大鼠血清胰岛素活性升高(P < 0.05或P < 0.01)，中等强度运动组大鼠血清胰岛素抵抗指数降低(P < 0.01)；高强度间歇运动组大鼠血清胰岛素活性高于中等强度运动组(P < 0.01)，两组间其余血清指标检测值比较差异无显著性意义(P > 0.05)。 2.5 运动干预后各组大鼠骨骼肌形态学观察各组大鼠骨骼肌苏木精-伊红染色结果，见图4。正常对照组骨骼肌切面完整，骨骼肌组织横切片的细胞形态完整，蓝色细胞核清晰可见，肌细胞被白色的结缔组织隔开，形态较好，肌细胞排列较为紧密。糖尿病对照组肌细胞之间排列松散，组织形态不规则，肌纤维内部空洞较多。相对于糖尿病对照组，中等强度运动组肌纤维间隙变小，肌纤维内部空洞变少，细胞结构趋于完整；高强度间歇运动组肌细胞之间排列松散，组织形态不规则，肌纤维内部空洞较多。提示中等强度的有氧运动可改善骨骼肌形态，而高强度间歇运动破坏了骨骼肌形态，对肌细胞造成损伤。 2.6 运动干预后各组大鼠骨骼肌羧酸酯酶1及炎症因子表达的比较 2.6.1 骨骼肌羧酸酯酶1及炎症因子mRNA表达与正常对照组相比，糖尿病对照组大鼠骨骼肌羧酸酯酶1、NEK7、白细胞介素18 mRNA表达升高(P < 0.01或P < 0.05)；与糖尿病对照组比较，中等强度运动组大鼠骨骼肌NEK7 mRNA表达降低(P < 0.01)，高强度间歇运动组大鼠骨骼肌"

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