Yüksek Glukoza Bağlı Vasküler Endotelyal Disfonksiyonda Resveratrolün Vazoprotektif Mekanizmaları: Bir in vitro Diyabet Modeli

Year 2025, Volume: 8 Issue: 3, 339 - 348, 22.10.2025

Gülşen Çelebi , Semil Selcen Göçmez , Ebru Serin , Muhammed Emin Emet , Tijen Utkan

https://doi.org/10.53446/actamednicomedia.1736837

Abstract

Amaç: Diyabetes mellitus, mikro ve makrovasküler komplikasyonlarla ilişkili hiperglisemi ile karakterizedir. Bu çalışma, yüksek glukozun diyabetes mellitustaki vasküler endotelyal disfonksiyon (VED) mekanizmaları üzerindeki etkilerini bir in vitro diyabet modeli kullanarak değerlendirmeyi ve daha önce in vivo olarak vasküler yanıtları iyileştirdiği gösterilen resveratrolün, yüksek glukoz ortamında faydalı etkilerini hangi mekanizmalarla gösterdiğini aydınlatmayı amaçlamıştır.
Yöntem: İzole sıçan torasik aort halkaları, normal glukoz (NG), HG (44 mM), HG + 10 µM resveratrol (HG+Resv) veya yüksek sükroz (HS) tamponlarında 2 saat inkübe edildi. Endotele bağımlı (karbakol) ve -bağımsız (SNP) gevşeme ile fenilefrin (Phe) kaynaklı kasılma yanıtları değerlendirildi. Resveratrolün mekanizmalarını araştırmak için, endotele bağımlı gevşemeler, L-NAME, metilen mavisi, indometasin, tetraetilamonyum, glibenklamid ve 4-aminopiridin ile 2 saatlik inkübasyon sonrası ayrı ayrı kaydedildi.
Bulgular: KCl ve SNP'ye verilen yanıtlar tüm gruplarda benzerken, HG karbakol kaynaklı endotele bağımlı gevşemeyi anlamlı ölçüde bozdu ve Phe kaynaklı kasılmayı artırdı. Resveratrol ile birlikte inkübasyon, hem karbakol gevşemesini hem de Phe kasılmasını NG seviyelerine doğru anlamlı ölçüde düzeltti. HS inkübasyonu NG'ye benzer yanıtlar verdi, bu da bozulmuş gevşemenin hiperozmolaliteden bağımsız olduğunu gösterdi. Ayrıca, L-NAME ve metilen mavisi, HG+Resv grubundaki karbakol gevşemesini anlamlı ölçüde baskıladı; tetraetilamonyum ve 4-aminopiridin de benzer etki gösterdi. Buna karşılık, indometasin ve glibenklamidin anlamlı bir etkisi olmadı, bu da PGI2 ve KATP için sınırlı roller olduğunu düşündürdü.
Sonuç: Resveratrol, NO-sGC-cGMP yolunu modüle ederek ve KCa ile KV kanallarını aktive ederek yüksek glukoza bağlı VED'i önlerken, artan kasılma yanıtlarını da azaltmaktadır. Bu bulgular, resveratrolün diyabetik vasküler komplikasyonlara karşı potansiyel bir koruyucu ajan olduğunu vurgulamaktadır.

Keywords

resveratrol , yüksek glukoz , hiperglisemi , torasik aorta , vasküler endotel disfonksiyon

Project Number

The authors affirm that no financial resources or grants were obtained for the present study.

Vasculoprotective Mechanisms of Resveratrol in High Glucose-Induced Vascular Endothelial Dysfunction: An in vitro Model of Diabetes

Abstract

Objective: Diabetes mellitus is characterized by hyperglycemia, which is associated with micro- and macrovascular complications. This study aimed to evaluate the effects of high glucose on the mechanisms of vascular endothelial dysfunction (VED) in diabetes mellitus using an in vitro diabetes model, and to elucidate the mechanisms by which resveratrol, previously shown to improve vascular responses in vivo, exerts its beneficial effects in a high glucose environment.
Methods: Isolated rat thoracic aortic rings were incubated for 2 hours in normal glucose (NG), HG (44 mM), HG+10µM resveratrol (HG+Resv), or high sucrose (HS) buffers. Endothelium-dependent (carbachol) and -independent (SNP) relaxation, and phenylephrine (Phe)-induced contraction responses were assessed. To investigate the mechanisms of resveratrol, endothelium-dependent relaxations were recorded separately following a 2-hour incubation with L-NAME, methylene blue, indomethacin, tetraethylammonium, glibenclamide, and 4-aminopyridine.
Results: While responses to KCl and SNP were similar in all groups, HG significantly impaired carbachol-induced endothelium-dependent relaxation and enhanced Phe-induced contraction. Resveratrol co-incubation significantly restored both carbachol relaxation and Phe contraction towards NG levels. HS incubation yielded responses similar to NG, indicating impaired relaxation was independent of hyperosmolality. Furthermore, L-NAME and methylene blue significantly suppressed carbachol relaxation in the HG+Resv group, as did tetraethylammonium and 4-aminopyridine. Conversely, indomethacin and glibenclamide had no significant effect, suggesting limited roles for PGI2 and KATP.
Conclusion: Resveratrol prevents high glucose-induced VED by modulating the NO-sGC-cGMP pathway and activating KCa and KV channels, while also diminishing enhanced contractile responses. These findings highlight resveratrol's potential as a protective agent against diabetic vascular complications.

Keywords

resveratrol , high glucose , hyperglycemia , thoracic aorta , vascular endothelial dysfunction

Ethical Statement

This study complies with the regulation on the welfare and protection of animals used for experiments and other scientific purposes, publicized in Turkey. Ethical approval was granted by the Kocaeli University Animal Experiments Local Ethics Committee with decision number 11/9-2017 and approval date 30/11/2017.

Project Number

The authors affirm that no financial resources or grants were obtained for the present study.

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