Polikistik Over Sendromu Modeli Oluşturulan Sıçanlarda Üridinin Beslenme ile İlişkili Moleküller Üzerine Etkisi

Öz

Polikistik Over Sendromu (PKOS), üreme çağındaki kadınların yaklaşık %10'unu etkileyen, infertilite, insülin direnci ve hiperandrojenizm ile karakterize karmaşık hormonal ve metabolik bir bozukluktur. Enerji dengesini etkileyen leptin, nesfatin-1 ve oreksin-A gibi peptitler PKOS patofizyolojisinde de kritik rol oynamaktadır. Üridin nükleozidinin bu peptitler üzerinde düzenleyici bir etkisi olabileceği de bilinmektedir. Bu çalışmanın amacı PKOS modeli oluşturulmuş sıçanlarda üridin uygulanmasının nesfatin-1, oreksin-A ve leptin gibi beslenme ile ilişkili moleküller üzerine etkisini incelemektir. Bu çalışmada; 8-10 haftalık, 200-300 gram ağırlığında 35 adet dişi Sprague-Dawley sıçan kullanılmıştır. PKOS modelini indüklemek için sıçanlara 21 gün boyunca her gün 60 mg/kg/ml dozunda dehidroepiandrosteron (DHEA) subkutan yolla uygulanmıştır. 21 günlük sürenin ardından, farklı üridin dozları (250 veya 500 mg/kg/ml) bir östrus döngüsüne (5 gün) eşdeğer sürede ilgili gruplara intraperitonal yolla uygulanmıştır. Dekapitasyon sonrası kan örnekleri santrifüj edilerek serumları toplanmıştır. Elde edilen serumlardan ELISA yöntemi ile oreksin-A, nesfatin-1 ve leptin düzeyleri tayin edilmiştir. Gruplar arası karşılaştırmalarda Tek Yönlü ANOVA (One-Way ANOVA) ve ardından post-hoc Holm-Sidak testi kullanılmış; p<0,05 değeri anlamlı kabul edilmiştir. PKOS grubunda azalan oreksin-A ve artan leptin seviyelerinin, üridin tedavisi ile anlamlı şekilde değiştiği gözlemlenmiştir. Nesfatin-1 seviyeleri ise gruplar arasında belirgin bir değişim göstermemiştir. Sonuç olarak, PKOS'ta bozulan oreksin-leptin dengesinin üridin ile modüle edilmesi, sendromun metabolik komplikasyonlarının tedavisinde yeni bir bakış açısı sunmaktadır.

Anahtar Kelimeler

• Polikistik over sendromu
• Üridin
• Nesfatin-1
• Oreksin-A
• Leptin

Destekleyen Kurum

Bursa Uludağ Üniversitesi

Proje Numarası

TGA1-2025-2098

Etik Beyan

Bu çalışma için Bursa Uludağ Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu'ndan onay alınmıştır (Karar no: 2025-15/10)

Teşekkür

Bu çalışma Bursa Uludağ Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir [TGA1-2025-2098].

The Modulatory Role of Uridine on Nutrition-Related Molecules in a Rat Model of Polycystic Ovary Syndrome

Öz

Polycystic Ovary Syndrome (PCOS) is a complex hormonal and metabolic disorder affecting approximately 10% of women of reproductive age and is characterized by infertility, insulin resistance, and hyperandrogenism. Peptides involved in energy homeostasis, such as leptin, nesfatin-1, and orexin-A, also play critical roles in the pathophysiology of PCOS. It has been suggested that the nucleoside uridine may exert regulatory effects on these peptides. The aim of this study was to investigate the effects of uridine on nesfatin-1, orexin-A, and leptin in a rat model of PCOS. In this study, 35 female Sprague-Dawley rats aged 8-10 weeks and weighing 200-300g were used. To induce the PCOS model, rats received subcutaneous injections of dehydroepiandrosterone at a dose of 60mg/kg/ml for 21 consecutive days. Following this period, uridine was administered intraperitoneally at doses of 250 or 500mg/kg/ml for a duration equivalent to one estrous cycle (5days) in the relevant groups. After decapitation, blood samples were collected, centrifuged, and serum samples were obtained. Serum levels of orexin-A, nesfatin-1, and leptin were measured using ELISA. Intergroup comparisons were performed using one-way analysis of variance, followed by the Holm-Sidak post hoc test. p<0.05 was considered statistically significant. The results demonstrated that decreased orexin-A and increased leptin levels observed in the PCOS group were significantly altered following uridine treatment. In addition, nesfatin-1 levels did not show a significant difference among the groups. In conclusion, modulation of disrupted orexin-leptin balance by uridine in PCOS may provide a novel perspective for management of metabolic complications associated with the syndrome.

Anahtar Kelimeler

• Polycystic ovary syndrome
• Uridine
• Nesfatin-1
• Orexin-A
• Leptin

Destekleyen Kurum

Bursa Uludağ University

Proje Numarası

TGA1-2025-2098

Etik Beyan

The study was approved by the Bursa Uludağ University Local Ethics Committee on Animal Research under decision number 2025-15/10.

Teşekkür

The research leading to these results received funding from Bursa Uludağ University Scientific Research Projects Unit under Grant Agreement No [TGA1-2025-2098].

Kaynakça

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