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维生素D和运动可改善糖尿病大鼠的血管内皮生长因子-B(VEGF-B)生成及胰岛素样生长因子-1(IGF-1)水平:对miR-1抑制作用的见解

Vitamin D and exercise improve VEGF-B production and IGF-1 levels in diabetic rats: insights the role of miR-1 suppression.

作者信息

Mazaheri Fatemeh, Hoseini Rastegar, Gharzi Ahmad

机构信息

Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran.

Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, P.O.Box. 6714414971, Kermanshah, Iran.

出版信息

Sci Rep. 2025 Jan 8;15(1):1328. doi: 10.1038/s41598-024-81230-3.

DOI:10.1038/s41598-024-81230-3
PMID:39779732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11711202/
Abstract

BACKGROUND

Type 2 Diabetes Mellitus (T2DM) is closely associated with the development of vascular damage in the heart. In this study, the researchers aimed to determine whether Aerobic Training (AT) and Vitamin D supplementation (Vit D) could alleviate heart complications and vascular damage caused by diabetes. The effects of an eight-week AT program and Vit D on the expression of miR-1, IGF-1 genes, and VEGF-B in the cardiomyocytes of rats with T2DM.

METHODS

This study was an experimental investigation. Fifty male Wistar rats were divided into 2 groups Non-Diabetic Obese Control (NC; n = 10), and diabetic (n = 40). The rats were then randomly divided into four groups: AT plus Vit D (AT + Vit D; n-=10), AT (n = 10), Vit D (Vit D; n = 10), and Control Diabetic (C; n = 10). The exercise groups underwent treadmill training for 8 weeks at an aerobic intensity equal to 50-60% of their maximal oxygen uptake (VO2max), which corresponded to a speed of 15-25 m/min at a 0% incline, for 30-60 min per day, 5 days per week. The Vit D and AT + Vit D groups received 5,000 international units (IU) of Vitamin D (combined with sesame oil) per week via a single-dose injection. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test for multiple comparisons among the groups. Paired data were analyzed using paired t-tests.

RESULTS

The results showed that BW, BMI, and FI significantly decreased in the AT + Vit D (p = 0.001 for all variables), AT (p = 0.001 for all variables), and Vit D (p = 0.001 for all variables) groups compared to baseline. In contrast, BW, BMI, and FI increased in the C (p = 0.001, p = 0.006, p = 0.020, respectively) and NC (p = 0.001 for all variables) groups. Significant differences were observed between the groups in terms of visceral fat, insulin, glucose, and HOMA-IR (p = 0.001 for all variables). Serum 25-hydroxyvitamin D levels varied significantly among the groups (p = 0.002). The AT + Vit D group showed significantly increased VEGF-B (p = 0.001 for both comparisons), upregulated IGF-1 (p = 0.001 for both comparisons), and downregulated miR-1 (p = 0.001 for both comparisons) compared to the AT and Vit D groups, respectively.

CONCLUSIONS

AT and Vit D increased the expression of IGF-1 and VEGF-B in the heart of T2DM rats while decreasing the expression of miR-1. These effects were more pronounced when AT and Vit D were combined. The study concludes that the combination of AT and Vit D has cardio-protective effects in T2DM rats, counteracting abnormal angiogenesis induced by diabetes. These effects are mediated, at least in part, by the upregulation of IGF-1 and VEGF-B, and the downregulation of miR-1.

摘要

背景

2型糖尿病(T2DM)与心脏血管损伤的发生密切相关。在本研究中,研究人员旨在确定有氧运动训练(AT)和补充维生素D(Vit D)是否可以减轻糖尿病引起的心脏并发症和血管损伤。为期八周的AT计划和Vit D对T2DM大鼠心肌细胞中miR-1、IGF-1基因和VEGF-B表达的影响。

方法

本研究为实验性调查。将50只雄性Wistar大鼠分为2组,非糖尿病肥胖对照组(NC;n = 10)和糖尿病组(n = 40)。然后将大鼠随机分为四组:AT加Vit D组(AT + Vit D;n = 10)、AT组(n = 10)、Vit D组(Vit D;n = 10)和糖尿病对照组(C;n = 10)。运动组在有氧强度相当于其最大摄氧量(VO2max)的50 - 60%的条件下进行8周的跑步机训练,这相当于在0%坡度下速度为15 - 25米/分钟,每天30 - 60分钟,每周5天。Vit D组和AT + Vit D组每周通过单剂量注射接受5000国际单位(IU)的维生素D(与芝麻油混合)。数据采用单因素方差分析(ANOVA),随后进行Tukey事后检验以进行组间多重比较。配对数据采用配对t检验进行分析。

结果

结果显示,与基线相比,AT + Vit D组(所有变量p = 0.001)、AT组(所有变量p = 0.001)和Vit D组(所有变量p = 0.001)的体重(BW)、体重指数(BMI)和脂肪指数(FI)显著降低。相比之下,C组(分别为p = 0.001、p = 0.006、p = 0.020)和NC组(所有变量p = 0.001)的BW、BMI和FI增加。各组在内脏脂肪、胰岛素、葡萄糖和稳态模型评估的胰岛素抵抗(HOMA-IR)方面存在显著差异(所有变量p = 0.001)。各组血清25-羟维生素D水平差异显著(p = 0.002)。与AT组和Vit D组相比,AT + Vit D组的VEGF-B显著增加(两次比较p = 0.001),IGF-1上调(两次比较p = 0.001),miR-1下调(两次比较p = 0.001)。

结论

AT和Vit D增加了T2DM大鼠心脏中IGF-1和VEGF-B的表达,同时降低了miR-1的表达。当AT和Vit D联合使用时,这些作用更为明显。该研究得出结论,AT和Vit D的联合应用对T2DM大鼠具有心脏保护作用,可抵消糖尿病诱导的异常血管生成。这些作用至少部分是由IGF-1和VEGF-B的上调以及miR-1的下调介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8313/11711202/20c6e2daa521/41598_2024_81230_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8313/11711202/02bd4a2259c6/41598_2024_81230_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8313/11711202/20c6e2daa521/41598_2024_81230_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8313/11711202/02bd4a2259c6/41598_2024_81230_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8313/11711202/20c6e2daa521/41598_2024_81230_Fig2_HTML.jpg

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