Sıçanlarda monokrotalinle oluşturulmuş pulmoner arteriyel hipertansiyon modelinde alamandin ve melatonin'in etkilerinin araştırılması
Küçük Resim Yok
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: PAH güncel tedavilere rağmen progresif ve fatal seyretmektedir. Çalışmamızda, kardiyovasküler hastalıklarda faydalı etkileri daha önce gösterilen ALA, MEL ve ALAMEL kombinasyonunun PAH'taki olası koruyucu etkilerinin karşılaştırılması amaçlandı. Gereç ve Yöntem: 10 haftalık erkek sıçanlar, basit randomize olarak kontrol (n=10), MCT (n=12), ALA (n=12), MEL (n=12) ve ALAMEL (n=12) gruplarına ayrıldı. 1. gün 60 mg/kg tek doz sc MCT ile PAH oluşturulurken; 1-35. günler arasında ALA grubuna 50 ?g/kg/gün ip ALA, MEL grubuna 10 mg/kg/gün ip MEL ve ALAMEL grubuna ise ALAMEL kombinasyonu uygulandı. Deney sonunda ekokardiyografik ve invazif hemodinamik ölçümler yapıldı. Kalp ve akciğer dokuları alınarak morfometrik, histopatolojik, ELISA ve western blot analizleri gerçekleştirildi. Bulgular: RV/LV, MCT grubunda artarken; ALA ve ALAMEL gruplarında azalmış bulundu. RVSP, MCT grubunda artarken; MEL grubunda düşme eğiliminde bulundu. MCT grubunda RV/LV+IVS artmış olup; MEL grubunda azalmış bulundu. Tüm tedavi gruplarında, inflamatuvar infiltrasyonda, TIM kalınlığı (p<0,0001) ile PCNA ve ?-SMA immünoreaktivitesinde azalma izlendi. Histopatolojik iyileşme MEL ve ALAMEL gruplarında ALA grubuna göre daha belirgindi. Artan LOX aktivitesi, tüm tedavi gruplarında MCT grubuna kıyasla azalırken; bu azalışın MEL grubunda ALA grubuna göre daha belirgin olduğu bulundu. Sonuçlar: ALA ve özellikle MEL'in antiinflamatuvar, antiproliferatif ve antiremodeling etkileriyle PAH gelişimini azalttığı, ALAMEL kombinasyonunun ise ek fayda sağlamadığı bulundu. ALA ve özellikle MEL'in, LOX inhibisyonuyla ECM remodelingini azaltmasının PAH'ın önlenmesinde önemli olduğu düşünülmektedir. Sonuçlarımızı destekleyecek ileri çalışmalara ihtiyaç vardır.
Aim: PAH has a progressive and fatal course despite current treatments. We aimed to compare the possible protective effects of ALA, MEL, and ALAMEL combination, whose beneficial effects in cardiovascular diseases have been shown before, in PAH. Material and Method: 10-week-old male rats were randomly divided into control (n=10), MCT (n=12), ALA (n=12), MEL (n=12) and ALAMEL (n=12) groups. PAH was induced by 60 mg/kg single dose sc MCT on day 1; 50 ?g/kg/day ip ALA, 10 mg/kg/day ip MEL and ALAMEL combination were administered to the ALA, MEL and ALAMEL groups (respectively) between days 1-35. Echocardiographic and invasive hemodynamic measurements were performed. Hearts and lungs were taken and morphometric, histopathological, ELISA and western blot analyzes were performed. Results: RV/LV was decreased in the ALA and ALAMEL groups compared to the MCT group. RVSP was tended to reduce and RV/LV+IVS was reduced in the MEL group. Inflammatory infiltration, TIM thickness, immunoreactivity of PCNA and ?-SMA were decreased in all treatment groups. Histopathological improvement in the MEL and ALAMEL groups were higher compared to the ALA group. LOX activity was reduced in all treatment groups; especially in the MEL group. Conclusion: ALA and especially MEL reduced the development of PAH with antiinflammatory, antiproliferative and antiremodeling effects, while combination treatment did not provide additional benefit. The reduction of ECM remodeling by LOX inhibition by ALA, and especially MEL, is thought to be important in the prevention of PAH. Further studies are needed to support our results.
Aim: PAH has a progressive and fatal course despite current treatments. We aimed to compare the possible protective effects of ALA, MEL, and ALAMEL combination, whose beneficial effects in cardiovascular diseases have been shown before, in PAH. Material and Method: 10-week-old male rats were randomly divided into control (n=10), MCT (n=12), ALA (n=12), MEL (n=12) and ALAMEL (n=12) groups. PAH was induced by 60 mg/kg single dose sc MCT on day 1; 50 ?g/kg/day ip ALA, 10 mg/kg/day ip MEL and ALAMEL combination were administered to the ALA, MEL and ALAMEL groups (respectively) between days 1-35. Echocardiographic and invasive hemodynamic measurements were performed. Hearts and lungs were taken and morphometric, histopathological, ELISA and western blot analyzes were performed. Results: RV/LV was decreased in the ALA and ALAMEL groups compared to the MCT group. RVSP was tended to reduce and RV/LV+IVS was reduced in the MEL group. Inflammatory infiltration, TIM thickness, immunoreactivity of PCNA and ?-SMA were decreased in all treatment groups. Histopathological improvement in the MEL and ALAMEL groups were higher compared to the ALA group. LOX activity was reduced in all treatment groups; especially in the MEL group. Conclusion: ALA and especially MEL reduced the development of PAH with antiinflammatory, antiproliferative and antiremodeling effects, while combination treatment did not provide additional benefit. The reduction of ECM remodeling by LOX inhibition by ALA, and especially MEL, is thought to be important in the prevention of PAH. Further studies are needed to support our results.
Açıklama
Anahtar Kelimeler
Eczacılık ve Farmakoloji, Pharmacy and Pharmacology
