TY  - JOUR
T1  - Yüksek Glukoza Bağlı Vasküler Endotelyal Disfonksiyonda Resveratrolün Vazoprotektif Mekanizmaları: Bir in vitro Diyabet Modeli
TT  - Vasculoprotective Mechanisms of Resveratrol in High Glucose-Induced Vascular Endothelial Dysfunction: An in vitro Model of Diabetes
AU  - Göçmez, Semil Selcen
AU  - Çelebi, Gülşen
AU  - Serin, Ebru
AU  - Emet, Muhammed Emin
AU  - Utkan, Tijen
PY  - 2025
DA  - October
Y2  - 2025
DO  - 10.53446/actamednicomedia.1736837
JF  - Acta Medica Nicomedia
JO  - Acta Med Nicomedia
PB  - Kocaeli Üniversitesi
WT  - DergiPark
SN  - 2717-8994
SP  - 339
EP  - 348
VL  - 8
IS  - 3
LA  - tr
AB  - 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.
KW  - resveratrol
KW  - yüksek glukoz
KW  - hiperglisemi
KW  - torasik aorta
KW  - vasküler endotel disfonksiyon
N2  - 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.
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UR  - https://doi.org/10.53446/actamednicomedia.1736837
L1  - https://dergipark.org.tr/tr/download/article-file/5031806
ER  -