糖尿病视网膜病变患者中山梨醇脱氢酶的表观遗传调控:DNA甲基化、组蛋白乙酰化和微小RNA-320

Epigenetic Regulation of Sorbitol Dehydrogenase in Diabetic Retinopathy Patients: DNA Methylation, Histone Acetylation and microRNA-320.

作者信息

Amin Ramzi, Permana Hikmat, Kartasasmita Arief Sjamsulaksan, Hilmanto Dany, Hidayat Rachmat

机构信息

Department of Ophthalmology, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia.

Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.

出版信息

Biologics. 2025 Apr 28;19:251-264. doi: 10.2147/BTT.S521519. eCollection 2025.

Abstract

PURPOSE

This study aimed to investigate the correlation between epigenetic markers and sorbitol dehydrogenase (SDH) levels in patients with type 2 diabetes and diabetic retinopathy (DR).

PATIENTS AND METHODS

We conducted a case control study on 40 patients with type 2 diabetes and DR and 40 patients with type 2 diabetes without DR. Clinical data and ophthalmological examinations were performed to confirm the presence or absence of DR. Blood samples were collected for the analysis of DNA methylation, histone acetylation, microRNA-320 levels, and SDH enzyme activity. The epigenetic markers were evaluated using enzyme linked immunosorbent modified assay. The data were analyzed using statistical tests, including Spearman correlation and multiple linear regression.

RESULTS

In patients with DR, there was a significant negative correlation between microRNA-320 levels and SDH enzyme activity (r=-0.968, p=0.000). No significant correlations were found between DNA methylation or histone acetylation and SDH activity. Multivariate analysis confirmed the strong negative correlation between microRNA-320 and SDH (r = -0.727, p=0.000), with microRNA-320 explaining 58.1% of the variance in SDH levels.

CONCLUSION

The findings suggest that microRNA-320 plays a crucial role in regulating SDH enzyme activity in patients with type 2 diabetes and DR. The development of microRNA-320-based therapies, such as miRNA mimics or antagomirs, may offer a novel approach to modulating SDH activity and mitigating the detrimental effects of the polyol pathway in DR. Further researches are needed to validate the results and mechanism underlying the correlation between epigenetic regulation SDH in DR.

摘要

目的

本研究旨在探讨2型糖尿病合并糖尿病视网膜病变(DR)患者表观遗传标记与山梨醇脱氢酶(SDH)水平之间的相关性。

患者与方法

我们对40例2型糖尿病合并DR患者和40例无DR的2型糖尿病患者进行了病例对照研究。进行临床数据和眼科检查以确认DR的存在与否。采集血样用于分析DNA甲基化、组蛋白乙酰化、微小RNA-320水平和SDH酶活性。使用酶联免疫吸附改良试验评估表观遗传标记。使用包括Spearman相关性和多元线性回归在内的统计检验分析数据。

结果

在DR患者中,微小RNA-320水平与SDH酶活性之间存在显著负相关(r=-0.968,p=0.000)。未发现DNA甲基化或组蛋白乙酰化与SDH活性之间存在显著相关性。多变量分析证实微小RNA-320与SDH之间存在强负相关(r = -0.727,p=0.000),微小RNA-320解释了SDH水平变异的58.1%。

结论

研究结果表明,微小RNA-320在调节2型糖尿病合并DR患者的SDH酶活性中起关键作用。基于微小RNA-320的疗法(如miRNA模拟物或反义寡核苷酸)的开发可能为调节SDH活性和减轻DR中多元醇途径的有害影响提供一种新方法。需要进一步研究来验证DR中表观遗传调控SDH之间相关性的结果和机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93d9/12048750/c988b02628bf/BTT-19-251-g0001.jpg

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