Deneysel serebral iskemi/reperfüzyon modeli oluşturulan sıçanlarda agomelatinin etkilerinin araştırılması
Küçük Resim Yok
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Bu çalışmada melatonerjik ve serotonerjik sistem aktivitesinde rol alan ve nörogenezi desteklediği bilinen Agomelatin'in, nöronlarda yoğun hasara neden olan Sİ/R sürecindeki etkilerinin araştırılması amaçlandı. Materyal Metod: Çalışmaya dahil edilen Sprague Dawley ırkı erkek sıçanlar kontrol, Sİ/R ve Sİ/R+Agomelatin (20 ve 40 mg/kg) olmak üzere dört gruba (n=10) ayrıldı. Kontrol dışındaki gruplarda 60 dakikalık Sİ uygulandı. Sİ'den bir saat sonra intraperitonal yolla Sİ/R grubuna hidroksietil selüloz, Sİ/R+Agomelatin gruplarına ise 20 ve 40 mg/kg Agomelatin uygulandı. Üç günlük R boyunca sıçanlara NDS, rotarod, yapışkan çıkarma ve kavrama gücü testleri yaptırıldı. Deney sonunda hayvanlar dekapite edilerek beyin dokuları alındı. Alınan beyin dokularında TTC boyama yöntemi ile infarkt alan, Western Blot yöntemi ile apoptoz (BCL-2 ve BAX) ve otofaji (Beclin-1, ATG5, ATG7 ve p62) proteinlerinin seviyeleri belirlendi. Elde edilen verilerin istatistiksel analizi yapıldı. Bulgular: Kontrol ve Sİ/R+Agomelatin gruplarının NDS skoru ve yapışkan çıkarma süresi, Sİ/R grubuna göre düşük; rotarodta kalma süresi ve kavrama gücü yüksekti (p<0.05). İnfarkt alanının Sİ/R grubunda, kontrol ve Sİ/R+Agomelatin gruplarına kıyasla büyük olduğu belirlendi (p<0.05). BCL-2, Beclin-1, ATG5 ve ATG7 protein seviyelerinin, Sİ/R+Agomelatin grubunda Sİ/R grubuna göre yüksek, BAX ve p62 protein seviyelerinin ise düşük olduğu tespit edildi (p<0.05). Sonuç: Agomelatin'in nörolojik defisit skorunu düşürdüğü görüldü. Davranış testlerinde de denge-motor koordinasyonu, somatosensör ve güç kaybını iyileştirdiği saptandı. İlaveten Agomelatin'in Sİ/R hasarının neden olduğu enfarktüs alanını azalttığı tespit edildi. Bunların yanı sıra apoptotik protein seviyelerinde apoptozu inhibe edecek yönde otofajik protein seviyelerinde otofajiyi indükleyecek yönde etkilediği tespit edildi.
Aim: In this study aimed to investigate the effects of Agomelatine, which plays a role in melatonergic and serotonergic system activity and is known to support neurogenesis, on the Cerebral Ischemia (CI)/Reperfusion (R) process, which causes intense damage to neurons. Materials and Methods Sprague Dawley male rats included in the study were divided into four groups (n = 10): control, CI/R and CI/R+Agomelatine (20 and 40 mg/kg). In groups other than control, 60-minute CI was applied. One hour after SI, hydroxyethyl cellulose was administered intraperitoneally to the CI/R group, and 20 and 40 mg/kg Agomelatine was administered to the SI/R+Agomelatine groups. During three days of R, the rats were subjected to NDS, rotarod, adhesive removal and gip strength tests. At the end of the experiment, the animals were decapitated and their brain tissues were taken. In the brain tissues taken, the levels of infarct area were determined by TTC staining method, and the levels of apoptosis (BCL-2 and BAX) and autophagy (Beclin-1, ATG5, ATG7 and p62) proteins were determined by Western Blot method. Statistical analysis of the data obtained was performed. Results: Control and Agomelatin groups than CI/R group, adhesive removal time and NDS score were lower; rotarod time and grip strength were higher (p<0.05). The infarct area was determined to be larger in the CI/R group compared to the control and SI/R+Agomelatine groups (p<0.05). BCL-2, Beclin-1, ATG5 and ATG7 protein levels were found to be higher in the SI/R+Agomelatine group compared to the CI/R group, and BAX and p62 protein levels were found to be lower (p<0.05). Conclusion: Agomelatine was observed to reduce the neurological deficit score. In behavioral tests, it was determined that it improved balance-motor coordination, somatosensory and strength loss. Additionally, it was determined that Agomelatine reduced the infarct area caused by CI/R injury. In addition, it was determined that it affected the apoptotic protein levels in a way that would inhibit apoptosis and the autophagic protein levels in a way that would induce autophagy.
Aim: In this study aimed to investigate the effects of Agomelatine, which plays a role in melatonergic and serotonergic system activity and is known to support neurogenesis, on the Cerebral Ischemia (CI)/Reperfusion (R) process, which causes intense damage to neurons. Materials and Methods Sprague Dawley male rats included in the study were divided into four groups (n = 10): control, CI/R and CI/R+Agomelatine (20 and 40 mg/kg). In groups other than control, 60-minute CI was applied. One hour after SI, hydroxyethyl cellulose was administered intraperitoneally to the CI/R group, and 20 and 40 mg/kg Agomelatine was administered to the SI/R+Agomelatine groups. During three days of R, the rats were subjected to NDS, rotarod, adhesive removal and gip strength tests. At the end of the experiment, the animals were decapitated and their brain tissues were taken. In the brain tissues taken, the levels of infarct area were determined by TTC staining method, and the levels of apoptosis (BCL-2 and BAX) and autophagy (Beclin-1, ATG5, ATG7 and p62) proteins were determined by Western Blot method. Statistical analysis of the data obtained was performed. Results: Control and Agomelatin groups than CI/R group, adhesive removal time and NDS score were lower; rotarod time and grip strength were higher (p<0.05). The infarct area was determined to be larger in the CI/R group compared to the control and SI/R+Agomelatine groups (p<0.05). BCL-2, Beclin-1, ATG5 and ATG7 protein levels were found to be higher in the SI/R+Agomelatine group compared to the CI/R group, and BAX and p62 protein levels were found to be lower (p<0.05). Conclusion: Agomelatine was observed to reduce the neurological deficit score. In behavioral tests, it was determined that it improved balance-motor coordination, somatosensory and strength loss. Additionally, it was determined that Agomelatine reduced the infarct area caused by CI/R injury. In addition, it was determined that it affected the apoptotic protein levels in a way that would inhibit apoptosis and the autophagic protein levels in a way that would induce autophagy.
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology
