Apelin, sakubitril/valsartan ve kombinasyonunun ratlarda doksorubisin ile indüklenen kalp yetmezliğinde profilaktik etkilerinin karşılaştırılması
Küçük Resim Yok
Tarih
2022
Yazarlar
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Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: KY miyokarddaki yapısal/fonksiyonel bozuklukların neden olduğu, ventriküler dolumun veya ejeksiyon fraksiyonun bozulmasına neden olan klinik bir sendromdur. Araştırmamızda, KVH'de olumlu etkileri bilinen apelin, SV ve kombinasyonunun KY'deki profilaktik etkilerinin karşılaştırılması amaçlandı. Gereç ve Yöntem: Çalışmada 4 aylık (250-300 g) toplam 50 adet Sprague Dawley ırkı erkek ratlar basit randomize tek kör olarak Kontrol (n=8), Dox (n=12), Apelin+Dox (n=10), SV+Dox (n=10) ve Apelin+SV+Dox (n=10) gruplarına ayrıldı. İki haftalık bir süre içinde 6X2,5 mg/kg (15 mg/kg) olacak şekilde ip yolla Dox verilerek KY modeli indüklendi. Aynı süre içinde Apelin grubuna ip yoldan 20 nmol/kg/gün apelin, SV+Dox grubuna perioral yoldan 68 mg/kg/gün SV ve Apelin+SV+Dox grubuna apelin, SV ve Dox uygulandı. Deney sonunda EKO ve invazif hemodinamik ölçümler yapıldı. Kalp, aort dokusu ve kan alınarak histopatoloji ve ELISA çalışıldı. Bulgular: Apelin+SV+Dox grubunda kalp ağırlığında iyileşme, SV+Dox ve Apelin+SV+Dox gruplarında mortalitede azalma, SV verilen her iki grupta da kontrol grubuna göre kalp hızında azalma tespit edildi. Dox, SV+Dox ve Apelin+SV+Dox grubunda sistolik kan basıncında azalma görüldü. Hem SV+Dox hem de Apelin+SV+Dox grubunda diyastolik ve ortalama kan basıncında azalma görüldü. Dox grubunda LVEF ve LVFS'de azalma, SV+Dox ve Apelin+SV+Dox grubunda ise artış tespit edildi. Dox grubunda dejenere kardiyomiyosit, vakuolizasyon, hemoraji, infiltrasyon, kollajen artışı, MMP-2 ve MMP-9 artış, tüm profilaktik gruplarda ise iyileşmeler görüldü. Biyokimyasal sonuçları açısından anlamlı bir değişiklik gözlenmedi. Sonuçlar: Dox ile indüklenen kalp yetmezliğinde SV daha fazla olmak üzere Apelin, SV ve kombinasyonun EKO ve histopatolojik olarak önemli iyileşmeler sağladığı bulundu. Sonuçlarımızı destekleyecek ileri çalışmalara ihtiyaç duyulmaktadır. Anahtar Kelimeler: Doksorubisin, apelin, sakubitril valsartan, kalp yetmezliği, ejeksiyon fraksiyonu, rat
Aim: HF is a clinical syndrome caused by structural/functional disorders in the myocardium, resulting in impaired ventricular filling or ejection fraction. In our study, it was aimed to compare the prophylactic effects of apelin, SV and their combination, which are known to have positive effects in CVD in HF. Material and Method: In the study, a total of 50 male Sprague Dawley rats aged 4 months (250-300 g) were simple randomized single-blind assigned to Control (n=8), Dox (n=12), Apelin+Dox (n=10), SV+Dox (n=10) and Apelin+SV+Dox (n=10) groups. The HF model was induced by ip administration of Dox at a rate of 6X2.5 mg/kg (15 mg/kg) over a two-week period. In the same period, 20 nmol/kg/day apelin was administered ip to the Apelin group, 68 mg/kg/day SV to the SV+Dox group periorally, and apelin, SV and Dox to the Apelin+SV+Dox group. ECHO and invasive hemodynamic measurements were performed at the end of the experiment. Heart, aortic tissue and blood were collected and histopathologically and ELISA were studied. Results: There was an improvement in heart weight in the Apelin+SV+Dox group, a decrease in mortality in the SV+Dox and Apelin+SV+Dox groups, and a decrease in heart rate in both groups given SV compared to the control group. A decrease in systolic blood pressure was observed in the Dox, SV+Dox and Apelin+SV+Dox groups. Diastolic and mean blood pressure were decreased in both SV+Dox and Apelin+SV+Dox groups. There was a decrease in LVEF and LVFS in the Dox group, and an increase in the SV+Dox and Apelin+SV+Dox groups. Degenerated cardiomyocyte, vacuolization, hemorrhage, infiltration, collagen increase, MMP-2 and MMP-9 increase were observed in the Dox group, while improvements were observed in all prophylactic groups. No significant change was observed in biochemical results. Conclusion: It was found that Apelin, SV and the combination, especially SV, provided significant improvements in ECHO and histopathologically in Dox-induced heart failure. Further studies are needed to support our results. Keywords: Doxorubicin, apelin, sacubitril/valsartan, heart failure, ejection fraction, rat
Aim: HF is a clinical syndrome caused by structural/functional disorders in the myocardium, resulting in impaired ventricular filling or ejection fraction. In our study, it was aimed to compare the prophylactic effects of apelin, SV and their combination, which are known to have positive effects in CVD in HF. Material and Method: In the study, a total of 50 male Sprague Dawley rats aged 4 months (250-300 g) were simple randomized single-blind assigned to Control (n=8), Dox (n=12), Apelin+Dox (n=10), SV+Dox (n=10) and Apelin+SV+Dox (n=10) groups. The HF model was induced by ip administration of Dox at a rate of 6X2.5 mg/kg (15 mg/kg) over a two-week period. In the same period, 20 nmol/kg/day apelin was administered ip to the Apelin group, 68 mg/kg/day SV to the SV+Dox group periorally, and apelin, SV and Dox to the Apelin+SV+Dox group. ECHO and invasive hemodynamic measurements were performed at the end of the experiment. Heart, aortic tissue and blood were collected and histopathologically and ELISA were studied. Results: There was an improvement in heart weight in the Apelin+SV+Dox group, a decrease in mortality in the SV+Dox and Apelin+SV+Dox groups, and a decrease in heart rate in both groups given SV compared to the control group. A decrease in systolic blood pressure was observed in the Dox, SV+Dox and Apelin+SV+Dox groups. Diastolic and mean blood pressure were decreased in both SV+Dox and Apelin+SV+Dox groups. There was a decrease in LVEF and LVFS in the Dox group, and an increase in the SV+Dox and Apelin+SV+Dox groups. Degenerated cardiomyocyte, vacuolization, hemorrhage, infiltration, collagen increase, MMP-2 and MMP-9 increase were observed in the Dox group, while improvements were observed in all prophylactic groups. No significant change was observed in biochemical results. Conclusion: It was found that Apelin, SV and the combination, especially SV, provided significant improvements in ECHO and histopathologically in Dox-induced heart failure. Further studies are needed to support our results. Keywords: Doxorubicin, apelin, sacubitril/valsartan, heart failure, ejection fraction, rat
Açıklama
Anahtar Kelimeler
Eczacılık ve Farmakoloji, Pharmacy and Pharmacology
