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给予糖尿病大鼠α-硫辛酸后,其主动脉壁中的肾上腺髓质素表达。

Adrenomedullin expression in aortic artery wall of diabetic rats given alpha lipoic acid.

机构信息

Vocational School of Health Services, Mersin University, Ciftlikkoy Campuse, 33343 Yenisehir, Mersin, Turkey.

Department of Cardiovascular Surgery, Faculty of Medicine, Mersin University, Mersin, Turkey.

出版信息

Pharmacol Rep. 2020 Aug;72(4):912-921. doi: 10.1007/s43440-020-00082-6. Epub 2020 Feb 27.

DOI:10.1007/s43440-020-00082-6
PMID:32103464
Abstract

BACKGROUND

Diabetes mellitus (DM) is a major health problem predisposing to cardiovascular diseases. The aim of this study was to investigate the effects of alpha lipoic acid (ALA) on both the arterial wall of diabetic rats and the adrenomedullin (ADM) gene expression.

METHODS

Twenty-four Wistar Albino rats were divided into three groups as Control, DM + S, and DM + ALA. For DM model, a single dose of 40 mg/kg streptozotocin, for DM + ALA group, 100 mg/kg/day/4 weeks was administered. Hematoxylin & Eosin (H&E) staining was done and vascular endothelial growth factor (VEGF) was detected by immunohistochemical analysis in the artery wall. Total damage score of vessel wall (endothelial cell damage, media layer smooth muscle cell damage, and internal elastic lamina damage) and H score (immunoreactivity intensity) were calculated. Expression of ADM gene was measured by qRT-PCR.

RESULTS

In DM + S group, Total damage score of vessel wall were detected by light microscopy. There were statistically significant differences between the groups Control/DM + S and DM + S/DM + ALA in terms of the vessel total damage score and H score (p < 0.005). ADM expression was increased threefold in both DM + S and DM + ALA groups compared to the control group (p < 0.05).

CONCLUSIONS

ALA may have positive effect on the vessel damage in diabetic rats. However, no significant decrease in ADM expression levels was observed in diabetic rats after ALA administration and we considered that the protective effect of ALA is independent of adrenomedullin. Further studies with different doses and durations of ALA administrations are required to investigate the changes in ADM expression.

摘要

背景

糖尿病(DM)是导致心血管疾病的主要健康问题。本研究旨在探讨α-硫辛酸(ALA)对糖尿病大鼠动脉壁和肾上腺髓质素(ADM)基因表达的影响。

方法

将 24 只 Wistar 白化大鼠随机分为三组:对照组、DM+S 组和 DM+ALA 组。DM 模型中,大鼠一次性腹腔注射 40mg/kg 链脲佐菌素,DM+ALA 组大鼠每天给予 100mg/kg/4 周。采用苏木精-伊红(H&E)染色和免疫组织化学分析检测动脉壁血管内皮生长因子(VEGF)的表达。计算血管壁总损伤评分(内皮细胞损伤、中膜平滑肌细胞损伤和内弹性膜损伤)和 H 评分(免疫反应强度)。采用 qRT-PCR 检测 ADM 基因的表达。

结果

在 DM+S 组中,通过光镜观察到血管壁总损伤评分。在血管壁总损伤评分和 H 评分方面,对照组/ DM+S 组和 DM+S/DM+ALA 组之间存在统计学差异(p<0.005)。与对照组相比,DM+S 组和 DM+ALA 组 ADM 表达均增加了三倍(p<0.05)。

结论

ALA 可能对糖尿病大鼠的血管损伤有积极作用。然而,我们发现糖尿病大鼠给予 ALA 后 ADM 表达水平没有明显降低,我们认为 ALA 的保护作用独立于肾上腺髓质素。需要进一步研究不同剂量和不同持续时间的 ALA 给药对 ADM 表达的影响。

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