Publication: Apelinin sıçanlarda kronik böbrek yetmezliği gelişimi, endotel disfonksiyonu ve kardiyak fonksiyonlar üzerine etkileri
Abstract
Amaç: Sıçanlarda oluşturulan kronik böbrek hastalığı (KBH) modelinde apelin reseptör (APJ) uyarımının böbrek fonksiyonları, böbrek ve kalp dokularındaki histopatolojik değişiklikler ile torasik aortanın (TA) endotel disfonksiyonu (ED) üzerine etkilerinin araştırılması hedeflenmiştir. Gereç ve Yöntem: Erkek Sprague Dawley sıçanlar taklit cerrahi (TC) grubuna veya 5/ 6 nefrektomi ile oluşturulan KBH gruplarına randomize edildiler. TC ve SF-KBH grupları subkütan serum fizyolojik (SF) alırken Apelin-KBH grubu 100 mcg/ gün Pyr-apelin13 ile Ala-apelin-KBH grubu da 100 mcg/ gün ala-apelin ile 8 hafta boyunca tedavi edildiler. Tedavi sonunda böbrek, kalp, serum ve idrar numunelerinde biyokimyasal, histopatolojik ve analizler yapıldı. Torasik aortaların (TA) karbakol ve apeline olan gevşeme yanıtları değerlendirildi. Bulgular: Ortalama arteryal basınç, serum BUN ve kreatinin düzeyleri SF-KBH grubuna kıyasla apelin-KBH ve ala-apelin-KBH gruplarında; proteinüri miktarıda ala-apelin-KBH grubunda azaldı. Serum IL-1β seviyeleri apelin-KBH ve ala-apelin-KBH gruplarında SF-KBH gruplarına kıyasla baskılandı. Histolojik değerlendirmelerde SF-KBH grubunda izlenen mezangial matriks ve inflamasyon skorlarındaki artış apelin ve ala-apelin tedavileri ile baskılandı. Torasik aortanın karbakol ve apeline olan gevşeme yanıtları SF-KBH grubunda bozulurken apelin ve ala-apelin-KBH gruplarında bu yanıtlar korundu. L-NAME ve ala-apelin pre-inkübasyonları ile bu yanıtlar bozulmakla birlikte apelin-KBH grubunda bozulmakla ala-apelin-KBH grubuna kıyasla daha iyi korunmuşlardı. Sonuç: APJ uyarımı böbrek fonksiyonlarındaki, histolojideki değişiklikleri ve ED bozulmayı kan basıncı ve inflamatuar yanıtı düzenleyerek korumuştur.
Objective: We investigated the effect of apelin receptor (APJ) stimulation on renal functions, histopathological changes in kidney and cardiac tissuses and endothelial dysfuntion (ED) of thoracis aortas (TA) in rats with chronic kidney disease (CKD). Materials and Methods: Male Sprague Dawley rats were randomized to sham operation (SO) or chronic kidney disease (CKD) groups after 5/ 6 nephrectomy. While SO-group and S-CKD groups received 0.9% saline subcutaneously, Apelin-CKD and Ala-apelin-CKD groups received pyr-apelin-13 or ala-apelin (each group 100 mcg/ day, s.c), respectively, for 8 weeks. Biochemical and histopathological analysis were performed on serum, urine, kidney and heart tissue samples. Vasorelaxation responses of TA to carbachol and apelin were evaluated. Results: While mean arterial blood pressure (MAP), BUN and creatinine decreased in both apelin-CKD and ala-apelin-CKD groups, proteinuria decreased by only ala-apelin treatment compared to the S-CKD group. Serum IL-1β levels were decreased in both apelin-CKD and ala-apelin-CKD groups compared to the S-CKD group. While mesangial matrix proliferation and inflammation scores of kidney tissues were decreased by both apelin and ala-apelin treatments, fibrosis scores of kidney and cardiac tiusses were similar in all groups. Vasorelaxation responses of TA to carbachol and apelin were preserved in the apelin and ala-apelin-CKD groups compared to the S-CKD group. Although preincubation with L-NAME and ala-apelin attenuated vasodilatatory responses to carbachol and apelin, these responses were much more preseverved in the apelin-CKD group compared to the ala-apelin-CKD group. Conclusion: Stimulation of APJ preserves impaired kidney functions, histopathological changes and ED through improvement of MAP and inflammatory responses.
Objective: We investigated the effect of apelin receptor (APJ) stimulation on renal functions, histopathological changes in kidney and cardiac tissuses and endothelial dysfuntion (ED) of thoracis aortas (TA) in rats with chronic kidney disease (CKD). Materials and Methods: Male Sprague Dawley rats were randomized to sham operation (SO) or chronic kidney disease (CKD) groups after 5/ 6 nephrectomy. While SO-group and S-CKD groups received 0.9% saline subcutaneously, Apelin-CKD and Ala-apelin-CKD groups received pyr-apelin-13 or ala-apelin (each group 100 mcg/ day, s.c), respectively, for 8 weeks. Biochemical and histopathological analysis were performed on serum, urine, kidney and heart tissue samples. Vasorelaxation responses of TA to carbachol and apelin were evaluated. Results: While mean arterial blood pressure (MAP), BUN and creatinine decreased in both apelin-CKD and ala-apelin-CKD groups, proteinuria decreased by only ala-apelin treatment compared to the S-CKD group. Serum IL-1β levels were decreased in both apelin-CKD and ala-apelin-CKD groups compared to the S-CKD group. While mesangial matrix proliferation and inflammation scores of kidney tissues were decreased by both apelin and ala-apelin treatments, fibrosis scores of kidney and cardiac tiusses were similar in all groups. Vasorelaxation responses of TA to carbachol and apelin were preserved in the apelin and ala-apelin-CKD groups compared to the S-CKD group. Although preincubation with L-NAME and ala-apelin attenuated vasodilatatory responses to carbachol and apelin, these responses were much more preseverved in the apelin-CKD group compared to the ala-apelin-CKD group. Conclusion: Stimulation of APJ preserves impaired kidney functions, histopathological changes and ED through improvement of MAP and inflammatory responses.