Sıçan deneysel multipl skleroz modelinde çinko eksikliği ve desteğinin hipokampus dokusundaki moleküler fonksiyonlar üzerine etkileri
Yükleniyor...
Dosyalar
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bu çalışmanın amacı, sıçan deneysel Multipl Skleroz (MS) Modelinde diyet çinko durumunun hipokampus dokusundaki ZnT3, NOGO-A, IL-6 ve SESN2 gen ifade düzeyleriyle hipokampal MDA ve GSH düzeylerini nasıl etkilediğinin araştırılmasıdır. Çalışma Selçuk Üniversitesi Deneysel Tıp Araştırma ve Uygulama Merkezinden temin edilen Wistar cinsi 46 adet erişkin erkek sıçanlar üzerinde gerçekleştirildi. Çalışma protokolü aynı merkezin Hayvan Etik Kurulu tarafından onaylandı (24.06.2022/2022-23). Çalışmada kullanılan hayvanlar 5 gruba ayrıldı: Kontroller grup 1 (n=6) ve grup 2 (n=10), deney grupları (Grup 3, 4 ve 5) n=10. Grup 1:Kontrol:8 hafta boyunca standart yemle beslendi. Grup 2:Sham-MS: Bu grubu oluşturan sıçanlara cuprizon'nun içinde çözünebileceği Karboksi-metil-selüloz (KMS) solüsyonu (saf su ile %1‟lik derişimde hazırlanan) günlük yem tüketiminin %1 (0,66 ± 0,06 gr/kg)'i oranında 8 hafta boyunca günlük olarak gavaj yoluyla verildi. Deneysel MS modeli grup 3, 4 ve 5'i oluşturan sıçanlara 8 hafta boyunca günlük yem tüketiminin %1 (0,66 ± 0,06 gr/kg)'i oranında cuprizonun, saf su ile %1‟lik derişimde hazırlandıktan sonra KMS solüsyonu içerisinde gavaj yoluyla verilerek oluşturuldu. Grup 3:MS:Standart yemle beslenen MS grubu. Grup 4:MS-Çinko Eksik Diyet: Bu gruptaki hayvanlar çalışmanın bitimine kadar çinko eksik (50 μg/kg) diyetle beslendiler. Grup 5:MS+ Çinko takviyeli Diyet: Bu gruptaki hayvanlara çalışmanın bitimine kadar intraperitoneal (i.p.) çinko çinko sülfat (5 mg/kg/gün) takviyesi yapıldı. Sekiz hafta süren uygulamaların bitiminden 24 saat sonra hayvanların tamamı genel anestezi altında sakrifiye edilerek hipokampus doku örnekleri alındı. Hipokampus dokusunda Real-Time-PCR yöntemi ile ZnT3, NOGO-A, IL-6 ve SESN2 gen ifadeleri tayin edildi. Yine hipokampus dokusunda MDA ve GSH düzeyleri ELISA yöntemiyle belirlendi. Hipokampus dokusundaki en yüksek MDA ve en düşük GSH düzeyleri ile yine hipokampal dokudaki en düşük ZnT3 ve en yüksek NOGO-A gen ifadesi Grup 3 ve 4'de elde edildi (p<0.05). Çinko desteği Grup 5'te hipokampus MDA değerleriyle NOGO-A gen ifadesi değerlerini önemli şekilde azaltırken (p<0.05) GSH değerleriyle ZnT3 gen ifadesi değerlerini önemli şekilde yükseltti (p<0.05). Hipokampus dokusundaki en yüksek IL-6 ve SESN2 gen ifadesi değerleri G3 ve G4'de elde edildi (p<0.05). Çinko desteği Grup 5'in hipokampal IL-6 ve SESN2 gen ifadesi değerlerini önemli şekilde azalttı(p<0.05).Mevcut çalışmanın sonuçları sıçan deneysel MS modelinde diyet çinko durumunun hipokampus dokusundaki bazı moleküler parametreleri önemli şekilde etkilediğini göstermektedir. Çinko desteği deneysel MS modelinde hipokampal dokuda ortaya çıkan patolojik süreçlerin önlenmesinde etkili olabilir.
The aim of this study is to investigate how dietary zinc status affects ZnT3, NOGO-A, IL-6 and SESN2 gene expression levels and hippocampal MDA and GSH levels in hippocampus tissue in a rat experimental Multiple Sclerosis (MS) Model. The study was carried out on 46 adult male Wistar rats obtained from Selçuk University Experimental Medicine Research and Application Center. The study protocol was approved by the Animal Ethics Committee of the same center (24.06.2022/2022-23). The animals used in the study were divided into 5 groups: Controls group 1(n=6) and group 2 (n = 10), experimental groups (Groups 3, 4 and 5) n = 10. Group 1:Control: For 8 weeks they were fed with standard feed.Group 2:Sham-MS: Carboxy-methyl-cellulose solution, in which cuprizone would be dissolved, was prepared with pure water at a concentration of 1% for the rats in this group. The prepared solution was given via gavage at a rate of 1% (0.66 ± 0,06 g/kg) of daily feed consumption. Applications were made daily for 8 weeks.MS was induced by giving cuprizone in KMS solution via gavage to the rats in Groups 3, 4 and 5, at a rate of 1% of the daily feed consumption for 8 weeks. Group 3:MS group fed with standard feed. MS Group 4: MS-Zinc Deficient Diet: Animals in this group were fed with a zinc deficient (50 μg/kg) diet until the end of the study. Group 5: MS+ Zinc-supplemented Diet: Animals in this group were supplemented with intraperitoneal (i.p.) zinc zinc sulfate (5 mg/kg/day) until the end of the study. 24 hours after the end of the eight-week application, all animals were sacrificed under general anesthesia and hippocampus tissue samples were taken. ZnT3, NOGO-A, IL-6 and SESN2 gene expressions were determined in hippocampus tissue by Real-Time-PCR method. Again, MDA and GSH levels in hippocampus tissue were determined by ELISA method. The highest MDA and lowest GSH levels in hippocampus tissue, the lowest ZnT3 and the highest NOGO-A gene expression in hippocampal tissue were obtained in Groups 3 and 4 (p<0.05). Zinc supplementation significantly decreased hippocampal MDA levels and NOGO-A gene expression values in Group 5 (p<0.05), while it significantly increased GSH levels and ZnT3 gene expression values (p<0.05). The highest IL-6 and SESN2 gene expression values in hippocampus tissue were obtained in G3 and G4 (p<0.05). Zinc supplementation significantly decreased the hippocampal IL-6 and SESN2 gene expression values of Group 5 (p<0.05). The results of the current study show that dietary zinc status significantly affects some molecular parameters in the hippocampus tissue in a rat experimental MS model. Zinc supplementation may be effective in preventing pathological processes occurring in hippocampal tissue in an experimental MS model.
The aim of this study is to investigate how dietary zinc status affects ZnT3, NOGO-A, IL-6 and SESN2 gene expression levels and hippocampal MDA and GSH levels in hippocampus tissue in a rat experimental Multiple Sclerosis (MS) Model. The study was carried out on 46 adult male Wistar rats obtained from Selçuk University Experimental Medicine Research and Application Center. The study protocol was approved by the Animal Ethics Committee of the same center (24.06.2022/2022-23). The animals used in the study were divided into 5 groups: Controls group 1(n=6) and group 2 (n = 10), experimental groups (Groups 3, 4 and 5) n = 10. Group 1:Control: For 8 weeks they were fed with standard feed.Group 2:Sham-MS: Carboxy-methyl-cellulose solution, in which cuprizone would be dissolved, was prepared with pure water at a concentration of 1% for the rats in this group. The prepared solution was given via gavage at a rate of 1% (0.66 ± 0,06 g/kg) of daily feed consumption. Applications were made daily for 8 weeks.MS was induced by giving cuprizone in KMS solution via gavage to the rats in Groups 3, 4 and 5, at a rate of 1% of the daily feed consumption for 8 weeks. Group 3:MS group fed with standard feed. MS Group 4: MS-Zinc Deficient Diet: Animals in this group were fed with a zinc deficient (50 μg/kg) diet until the end of the study. Group 5: MS+ Zinc-supplemented Diet: Animals in this group were supplemented with intraperitoneal (i.p.) zinc zinc sulfate (5 mg/kg/day) until the end of the study. 24 hours after the end of the eight-week application, all animals were sacrificed under general anesthesia and hippocampus tissue samples were taken. ZnT3, NOGO-A, IL-6 and SESN2 gene expressions were determined in hippocampus tissue by Real-Time-PCR method. Again, MDA and GSH levels in hippocampus tissue were determined by ELISA method. The highest MDA and lowest GSH levels in hippocampus tissue, the lowest ZnT3 and the highest NOGO-A gene expression in hippocampal tissue were obtained in Groups 3 and 4 (p<0.05). Zinc supplementation significantly decreased hippocampal MDA levels and NOGO-A gene expression values in Group 5 (p<0.05), while it significantly increased GSH levels and ZnT3 gene expression values (p<0.05). The highest IL-6 and SESN2 gene expression values in hippocampus tissue were obtained in G3 and G4 (p<0.05). Zinc supplementation significantly decreased the hippocampal IL-6 and SESN2 gene expression values of Group 5 (p<0.05). The results of the current study show that dietary zinc status significantly affects some molecular parameters in the hippocampus tissue in a rat experimental MS model. Zinc supplementation may be effective in preventing pathological processes occurring in hippocampal tissue in an experimental MS model.
Açıklama
Anahtar Kelimeler
Multipl Skleroz, Cuprizone, Hipokampus, Oksidatif Stres, Multiple Sklerosis, Cuprizon, Hippocampus, Oxidative Stres
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Atacak, A. (2024). Sıçan deneysel multipl skleroz modelinde çinko eksikliği ve desteğinin hipokampus dokusundaki moleküler fonksiyonlar üzerine etkileri. (Doktora Tezi). Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü, Konya.
