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白藜芦醇改善2型糖尿病诱导的大鼠膝关节软骨超微结构改变。

Resveratrol ameliorates type 2 diabetes mellitus-induced alterations to the knee joint articular cartilage ultrastructure in rats.

作者信息

El-Bidawy Mahmoud H, Omar Hussain Abo Bakr, Al-Ghamdi Sameer, Aldossari Khalid K, Haidara Mohamed A, Al-Ani Bahjat

机构信息

Department of BMS, Division of Physiology, College of Medicine, Prince Sattam Ibin Abdulaziz University, Al-Kharj, Saudi Arabia.

Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Ultrastruct Pathol. 2021 Mar 4;45(2):92-101. doi: 10.1080/01913123.2021.1882629. Epub 2021 Feb 11.

Abstract

Diabetes-induced osteoarthritis (OA) is a chronic inflammatory disease that damages the cartilage in the joints and could lead to disability. The protective effect of the antioxidant and anti-inflammatory agent, resveratrol, against alterations to the knee articular cartilage ultrastructure induced by type 2 diabetes mellitus (T2DM) associated with the inhibition of dyslipidemia, oxidative stress, and inflammation has not been investigated before. Therefore, we modeled OA in rats 10 weeks post diabetic induction using a high carbohydrate and fat diet and a single injection of streptozotocin (50 mg/kg body weight), and the protective group of rats started resveratrol (30 mg/kg; orally) treatment 2 weeks before diabetic induction and continued on resveratrol until the end of the experiment at week 12. Blood chemistry analysis confirmed hyperglycemia (elevated glucose and glycated hemoglobin, HbA1c), dyslipidemia (elevated triglyceride, cholesterol, and low-density lipoprotein-cholesterol), and upregulation of oxidative stress (malondialdehyde) and inflammatory (C-reactive protein and tumor necrosis factor-α) biomarkers in the model group. In addition, using light and electron microscopy examinations, we also observed in the model group substantial damage to the articular cartilage and profound chondrocyte and territorial matrix ultrastructural alterations such as chondrocytes with degenerated nucleus and mitochondria, scarce cytoplasmic processes, and absence of the fine fibrillar appearance of territorial matrix. Resveratrol pretreatment significantly (p ≤ 0.0029) but not completely protected from T2DM-induced OA. We conclude that resveratrol protects against alterations to the articular cartilage ultrastructure induced secondary to T2DM in rats, which is associated with the inhibition of glycemia, hyperlipidemia, and biomarkers of oxidative stress and inflammation.

摘要

糖尿病诱发的骨关节炎(OA)是一种慢性炎症性疾病,会损害关节软骨并可能导致残疾。抗氧化和抗炎剂白藜芦醇对2型糖尿病(T2DM)诱导的膝关节软骨超微结构改变的保护作用,以及与血脂异常、氧化应激和炎症抑制的相关性,此前尚未得到研究。因此,我们通过高碳水化合物和高脂肪饮食以及单次注射链脲佐菌素(50 mg/kg体重),在糖尿病诱导后10周建立大鼠OA模型,而保护组大鼠在糖尿病诱导前2周开始白藜芦醇(30 mg/kg;口服)治疗,并持续使用白藜芦醇直至实验第12周结束。血液化学分析证实模型组存在高血糖(血糖和糖化血红蛋白HbA1c升高)、血脂异常(甘油三酯、胆固醇和低密度脂蛋白胆固醇升高)以及氧化应激(丙二醛)和炎症(C反应蛋白和肿瘤坏死因子-α)生物标志物上调。此外,通过光学和电子显微镜检查,我们还在模型组中观察到关节软骨的严重损伤以及软骨细胞和区域基质超微结构的深刻改变,如软骨细胞核和线粒体退化、细胞质突起稀少以及区域基质缺乏细纤维外观。白藜芦醇预处理具有显著(p≤0.0029)但不完全的保护作用,可防止T2DM诱导的OA。我们得出结论,白藜芦醇可保护大鼠免受T2DM继发的关节软骨超微结构改变,这与血糖、高脂血症以及氧化应激和炎症生物标志物的抑制有关。

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