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表观遗传酶沉默调节蛋白-1和高迁移率族蛋白B1在糖尿病足溃疡患者中的新作用。

The emerging role of the epigenetic enzyme Sirtuin-1 and high mobility group Box 1 in patients with diabetic foot ulceration.

作者信息

Hafez Yasser Mostafa, El-Deeb Omnia Safwat, Atef Marwa Mohamed

机构信息

Lecturer of Internal Medicine, Internal Medicine Department, Faculty of Medicine, Tanta University, El Geesh street, Tanta, Egypt.

Lecturers of Medical Biochemistry, Medical Biochemistry Department, Faculty of Medicine, Tanta University, El Geesh street, Tanta, Egypt.

出版信息

Diabetes Metab Syndr. 2018 Nov;12(6):1065-1070. doi: 10.1016/j.dsx.2018.06.026. Epub 2018 Jul 5.

Abstract

BACKGROUND

Diabetic foot ulceration (DFU) is a serious diabetic complication that can progress to amputation and since SIRT1 regulates glucose metabolism, inflammation, and oxidative stress which are the major contributors in diabetic complications, So we aimed to discuss its role as an epigenetic biomarker in DFU and highlight its link to oxidative stress and inflammatory cytokines.

METHOD

60 DM patients were enrolled in the study, 30 without DFU and 30 with DFU in addition to 15 healthy subjects (control group). SIRT1 mRNA relative gene expression was assessed. Catalase activity, advanced glycation end products (AGEs), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6) and High mobility group box1 (HMGB1) levels were measured. DNA fragmentation was also performed.

RESULT

SIRT1 expression and catalase activity were significantly decreased in diabetic patients compared to control group with the lowest levels in DFU patients, TNFα, IL-6, HMGB 1 and AGEs levels were significantly higher in the diabetic patients compared to control group with the highest levels in DFU patients. DNA fragmentation was more profound in DFU patients.

CONCLUSION

The study revealed that SIRT1 mRNA expression can be considered as a novel biomarker in DFU being a major player involved in its pathogenesis.

摘要

背景

糖尿病足溃疡(DFU)是一种严重的糖尿病并发症,可发展至截肢。由于沉默信息调节因子1(SIRT1)调节葡萄糖代谢、炎症和氧化应激,而这些是糖尿病并发症的主要促成因素,因此我们旨在探讨其作为DFU表观遗传生物标志物的作用,并强调其与氧化应激和炎性细胞因子的联系。

方法

本研究纳入60例糖尿病患者,其中30例无DFU,30例有DFU,另外还有15名健康受试者(对照组)。评估SIRT1 mRNA相对基因表达。测量过氧化氢酶活性、晚期糖基化终产物(AGEs)、肿瘤坏死因子α(TNFα)、白细胞介素6(IL-6)和高迁移率族蛋白B1(HMGB1)水平。还进行了DNA片段化检测。

结果

与对照组相比,糖尿病患者的SIRT1表达和过氧化氢酶活性显著降低,DFU患者中最低。与对照组相比,糖尿病患者的TNFα、IL-6、HMGB 1和AGEs水平显著升高,DFU患者中最高。DFU患者的DNA片段化更为明显。

结论

该研究表明,SIRT1 mRNA表达可被视为DFU的一种新型生物标志物,是其发病机制中的主要参与者。

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