Sıçanlarda oluşturulan deneysel serebral iskemi-reperfüzyon modelinde dapagliflozin'in nöroprotektif etkilerinin araştırılması
Küçük Resim Yok
Tarih
2025
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Bu çalışmada, SGLT2 inhibitörü olan dapagliflozin'in (Dapa), serebral iskemi ile oluşturulan inme modelinde sıçanlardaki potansiyel nöroprotektif etkisini değerlendirmek amaçlandı. Materyal ve metot: 40 adet erkek Sprague Dawley sıçanı dört gruba ayrıldı (n=10): Sham, Sİ/R, Sİ/R + Dapa 1 mg/kg ve Sİ/R + Dapa 10 mg/kg. Sham grubuna çözücü, Dapa gruplarına ise 1 mg/kg ve 10 mg/kg dapa oral gavaj yoluyla 1 hafta verildi. Deney öncesinde tüm hayvanlara rotarod, yapışkan çıkarma ve güç testi gibi üç günlük davranış testlerinin ön eğitimi yapıldı. Sonrasında, 60 dakika fokal serebral iskemi operasyonu gerçekleştirildi ve 24 saatlik reperfüzyon sürecinin ardından nörolojik defisit skorlama (NDS) ve davranış testleri yapıldı. Çalışma sonrası infarkt alanı TTC boyama yöntemi ile belirlenmiştir. Bunun yanı sıra Western blot, ELISA ve oksidatif stres analizleri uygulanarak biyokimyasal değerlendirmeler gerçekleştirilmiştir. Bulgular: Dapa uygulaması, Sİ/R grubuna kıyasla NDS skorunu ve yapışkan çıkarma süresini azaltırken, güç kavrama ve rotarodta kalma süresini anlamlı şekilde artırmıştır (p <0.05). Ayrıca, infarkt alanını Sİ/R grubuna kıyasla belirgin şekilde azalttığı gözlemlenmiştir (p<0.05). Moleküler düzeyde BDNF, TrkB, p-AKT, p-PI3K ve BCL-2 protein seviyelerini artırırken, BAX ve Kaspaz-3 protein seviyelerini düşürmüştür (p<0.05). Ayrıca inflamatuvar medyatörlerden IL-1?, IL-6, TNF-? ve NLRP3 seviyelerinde anlamlı bir azalma sağlarken (p<0.05); oksidan-antioksidan parametrelerden SOD, CAT ve GSH-Px enzim seviyelerini artırmış, MDA seviyesini ise azaltmıştır (p<0.05). Sonuç: Bu çalışma, Dapa'nın serebral iskemiye karşı nöroprotektif etkiler sağladığını ortaya koymuştur. Sonuçlar, Dapa'nın serebral iskemi tedavisinde potansiyel bir terapötik ajan olarak değerlendirilebileceğini göstermektedir. Anahtar Kelimeler: Dapagliflozin, İnflamasyon, Nöroprotektif, Nörolojik defisit, Oksidatif stres, Serebral İskemi
Objective: This study aimed to evaluate the neuroprotective effects of dapagliflozin (Dapa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in a rat model of cerebral ischemia-induced stroke. Materials and method: Forty male Sprague-Dawley rats were divided into four groups (n=10): Sham, ischemia/reperfusion (I/R), I/R + Dapa 1 mg/kg, and I/R + Dapa 10 mg/kg. The Sham group received a vehicle, while Dapa groups were administered 1 mg/kg and 10 mg/kg dapa orally for one week. Pre-training on behavioral tests (rotarod, adhesive removal, and grip strength) was performed before the experiment. A 60-minute focal cerebral ischemia was induced, followed by a 24-hour reperfusion period. Neurological deficit scoring (NDS) and behavioral tests were conducted. Infarct area was assessed using TTC staining. Western blot, ELISA, and oxidative stress analyses were also performed. Results: Dapa treatment significantly reduced NDS scores and adhesive removal time, while increasing grip strength and rotarod performance compared to the I/R group (p<0.05). Infarct area was also significantly reduced in Dapa-treated groups (p<0.05). At the molecular level, Dapa increased BDNF, TrkB, p-AKT, p-PI3K, and BCL-2, while decreasing BAX and Caspase-3 (p<0.05). Additionally, inflammatory mediators (IL-1?, IL-6, TNF-?, NLRP3) were significantly reduced, and antioxidant enzymes (SOD, CAT, GSH-Px) were increased, while MDA levels decreased (p<0.05). Conclusion: Dapa demonstrated neuroprotective effects in cerebral ischemia, suggesting its potential as a therapeutic agent for stroke treatment. Keywords: Cerebral Ischemia, Dapagliflozin, Inflammation, Neuroprotective, Neurological deficit, Oxidative stress
Objective: This study aimed to evaluate the neuroprotective effects of dapagliflozin (Dapa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in a rat model of cerebral ischemia-induced stroke. Materials and method: Forty male Sprague-Dawley rats were divided into four groups (n=10): Sham, ischemia/reperfusion (I/R), I/R + Dapa 1 mg/kg, and I/R + Dapa 10 mg/kg. The Sham group received a vehicle, while Dapa groups were administered 1 mg/kg and 10 mg/kg dapa orally for one week. Pre-training on behavioral tests (rotarod, adhesive removal, and grip strength) was performed before the experiment. A 60-minute focal cerebral ischemia was induced, followed by a 24-hour reperfusion period. Neurological deficit scoring (NDS) and behavioral tests were conducted. Infarct area was assessed using TTC staining. Western blot, ELISA, and oxidative stress analyses were also performed. Results: Dapa treatment significantly reduced NDS scores and adhesive removal time, while increasing grip strength and rotarod performance compared to the I/R group (p<0.05). Infarct area was also significantly reduced in Dapa-treated groups (p<0.05). At the molecular level, Dapa increased BDNF, TrkB, p-AKT, p-PI3K, and BCL-2, while decreasing BAX and Caspase-3 (p<0.05). Additionally, inflammatory mediators (IL-1?, IL-6, TNF-?, NLRP3) were significantly reduced, and antioxidant enzymes (SOD, CAT, GSH-Px) were increased, while MDA levels decreased (p<0.05). Conclusion: Dapa demonstrated neuroprotective effects in cerebral ischemia, suggesting its potential as a therapeutic agent for stroke treatment. Keywords: Cerebral Ischemia, Dapagliflozin, Inflammation, Neuroprotective, Neurological deficit, Oxidative stress
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology
