Otozomal dominant polikistik böbrek hastalığında kallistatin, VEGF-A, TNF-α VE Nf-κB ile oksidatif stres arasındaki ilişkinin incelenmesi
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Dosyalar
Tarih
2021
Yazarlar
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Yayıncı
Hatay Mustafa Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Otozomal dominant polikistik böbrek hastalığı (ODPBH) böbrek parankimini etkileyen çoklu kistik lezyonlarla ve proteinlerdeki mutasyonlarla karakterize bir hastalıktır. ODPBH patogenezinde kist oluşumu nefronun herhangi bir yerinden gelişebilir ve başlangıçta tübül ile bağlantılıyken zamanla otonomi kazanır. Bu çalışmada amacımız ODPBH hastalarında kallistatin, TNF-α, VEGF-A, Nf-κB ve oksidatif stres arasındaki ilişkisinin incelenmesi ve hastalık patogenezindeki rolününün araştırılmasıdır. Çalışmaya glomerüler filtrasyon hızı (GFR) değerlerine göre 25 erken evre ODPBH (evre 1-2) ve 18 ileri evre ODPBH (evre 3-4) hasta ile 26 sağlıklı birey kontrol grubu olarak dahil edildi. Hastalarda manyetik rezonans görüntüleme yöntemi ile toplam böbrek hacmi ölçüldü. Rutin biyokimyasal parametreler, idrar mikroalbumin ve kreatinin düzeyleri spektrofotometrik yöntemle Total Antioksidan Status (TAS), Total Oksidan Status (TOS) düzeyleri ise kolorimetrik yöntemle otoanalizörde ölçüldü. Oksidatif Stres İndeksi (OSİ) TOS/TAS*100 şeklinde hesaplandı. Serum Kallistatin, VEGF-A, TNF-α ile Nf-кB protein düzeyleri ELISA yöntemi ile çalışıldı. Ayrıca serum Nf-кB protein düzeyleri Western Blot yöntemi ile de çalışıldı. Serum Kallistatin, VEGF-A ve TNF-α düzeyleri ile hesaplanmış OSİ değerleri ODPBH (evre 1-2) ve ODPBH (evre 3-4) hasta gruplarında kontrol grubuna göre anlamlı olarak yüksek saptandı. Kallistatin değerleri, TAS, GFR, idrar kreatinin ile negatif korelasyon; serum kreatinin, idrar albumin, spot idrarda protein/kreatinin değeri, Nf-κB, TNF-α ve VEGF-A ile pozitif korelasyon göstermiştir. Benzer şekilde Nf-κB ve TNF-α arasında pozitif korelasyon saptandı. Ayrıca serum Nf-κB protein düzeyleri Western Blot yöntemi ile tayin edildi. Hem enzim bağlı immünosorbent yöntem (ELISA) hem de Western Blot sonuçlarına göre serum Nf-κB düzeyleri ODPBH (evre 1-2) ve ODPBH (evre 3-4) gruplarında kontrol grubuna kıyasla anlamlı olarak yüksek bulundu. Bu çalışma ODPBH olan kişilerde serum kallistatin düzeylerini gösteren ilk çalışmadır. Tüm bu bulgular dikkate alındığında kallistatinin ODPBH patogenezinde anjiyogenezis, apoptozis ve inflamasyon süreçlerinde rol oynadığı söylenebilir.
Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by multiple cystic lesions affecting the kidney parenchyma and mutations in proteins. In ADPKD pathogenesis, cyst formation can develop from any part of the nephron and while initially connected with the tubule, it gains autonomy over time. Our aim in this study is to examine the relationship between kallistatin, TNF-α, VEGF-A, Nf-κB and oxidative stress in ADPKD patients and to investigate their role in disease pathogenesis. According to the glomerular filtration rate (GFR) values, 25 early-stage ADPKD (stage 1-2) and 18 advanced stage ADPKD (stage 3-4) patients and 26 healthy individuals as a control group were included in the study. Total renal volume was measured by magnetic resonance imaging method. Routine biochemical parameters, urine microalbumin and creatinine levels were measured by spectrophotometric method, Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) levels were measured by colorimetric method in autoanalyzer. Oxidative Stress Index (OSI) was calculated as TOS / TAS * 100. Serum Kallistatin, VEGF-A, TNF-α and Nf-κB protein levels were measured by ELISA method. Serum Nf-κB protein levels were also studied by Western Blot method. OSI values calculated with serum Kallistatin, VEGF-A and TNF-α levels were found to be significantly higher in ADPKD (stage 1-2) and ADPKD (stage 3-4) patient groups compared to the control group. Callistatin values, were negatively correlated; with TAS, GFR, urinary creatinine, serum creatinine, urine albumin, protein / creatinine value in spot urine, Nf-κB, TNF-α and VEGF-A were positively correlated. Similarly, a positive correlation was found between Nf-κB and TNF-α. In addition, serum Nf-κB protein levels were determined by western blot method. According to both ELISA and Western Blot results, serum Nf-κB levels were found to be significantly higher in ADPKD (stage 1-2) and ADPKD (stage 3-4) groups compared to the control group. This is the first study to show serum kallistatin levels in people with ADPKD. Considering all these findings, it can be said that callistatin plays a role in angiogenesis, apoptosis and inflammation processes in ADPKD pathogenesis.
Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by multiple cystic lesions affecting the kidney parenchyma and mutations in proteins. In ADPKD pathogenesis, cyst formation can develop from any part of the nephron and while initially connected with the tubule, it gains autonomy over time. Our aim in this study is to examine the relationship between kallistatin, TNF-α, VEGF-A, Nf-κB and oxidative stress in ADPKD patients and to investigate their role in disease pathogenesis. According to the glomerular filtration rate (GFR) values, 25 early-stage ADPKD (stage 1-2) and 18 advanced stage ADPKD (stage 3-4) patients and 26 healthy individuals as a control group were included in the study. Total renal volume was measured by magnetic resonance imaging method. Routine biochemical parameters, urine microalbumin and creatinine levels were measured by spectrophotometric method, Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) levels were measured by colorimetric method in autoanalyzer. Oxidative Stress Index (OSI) was calculated as TOS / TAS * 100. Serum Kallistatin, VEGF-A, TNF-α and Nf-κB protein levels were measured by ELISA method. Serum Nf-κB protein levels were also studied by Western Blot method. OSI values calculated with serum Kallistatin, VEGF-A and TNF-α levels were found to be significantly higher in ADPKD (stage 1-2) and ADPKD (stage 3-4) patient groups compared to the control group. Callistatin values, were negatively correlated; with TAS, GFR, urinary creatinine, serum creatinine, urine albumin, protein / creatinine value in spot urine, Nf-κB, TNF-α and VEGF-A were positively correlated. Similarly, a positive correlation was found between Nf-κB and TNF-α. In addition, serum Nf-κB protein levels were determined by western blot method. According to both ELISA and Western Blot results, serum Nf-κB levels were found to be significantly higher in ADPKD (stage 1-2) and ADPKD (stage 3-4) groups compared to the control group. This is the first study to show serum kallistatin levels in people with ADPKD. Considering all these findings, it can be said that callistatin plays a role in angiogenesis, apoptosis and inflammation processes in ADPKD pathogenesis.
Açıklama
Anahtar Kelimeler
Biyokimya, Biochemistry
