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去氢表雄酮对高糖诱导的氧化应激的肌腱细胞保护作用的体内外研究。

In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress.

机构信息

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.

出版信息

BMC Musculoskelet Disord. 2021 Jun 5;22(1):519. doi: 10.1186/s12891-021-04398-z.

DOI:10.1186/s12891-021-04398-z
PMID:34090401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8180149/
Abstract

BACKGROUND

Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons.

METHODS

Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined.

RESULTS

In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group.

CONCLUSIONS

DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

摘要

背景

脱氢表雄酮（DHEA）是一种肾上腺类固醇，具有抵抗糖尿病的保护作用。本研究旨在探讨 DHEA 对肌腱细胞和肌腱中高糖诱导的氧化应激的体外和体内保护作用。

方法

正常 Sprague-Dawley 大鼠的肌腱细胞在低糖（LG）或高糖（HG）培养基中培养，有或没有 DHEA。实验组为：对照组（LG 无 DHEA）、LG 加 DHEA、HG 无 DHEA 和 HG 加 DHEA。测定活性氧（ROS）产生、凋亡以及 NADPH 氧化酶（NOX）1 和 4 和白细胞介素 6（IL-6）的信使 RNA（mRNA）表达。此外，糖尿病大鼠分为对照组和 DHEA 注射组（DHEA 组）。测定 NOX1 和 NOX4 蛋白表达以及 NOX1、NOX4、IL-6、基质金属蛋白酶（MMP）-2、基质金属蛋白酶抑制剂（TIMP）-2 和 I 型和 III 型胶原的 mRNA 表达。

结果

在大鼠肌腱细胞中，DHEA 降低了 NOX1 和 IL-6 的表达、ROS 积累和凋亡细胞。在糖尿病大鼠跟腱中，DHEA 组的 NOX1 蛋白表达和 NOX1、IL-6、MMP-2、TIMP-2 和 III 型胶原的 mRNA 表达明显低于对照组，而 I 型胶原表达明显高于对照组。

结论

DHEA 在体外和体内均具有抗氧化和抗炎作用。此外，DHEA 改善了高糖条件下受影响的肌腱基质合成和转化。DHEA 是一种有潜力的预防糖尿病性肌腱病的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b090/8180149/9d0d15df1760/12891_2021_4398_Fig7_HTML.jpg
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