Ratlarda sepsise bağlı akut böbrek hasarının önlenmesindeuzak iskemik önkoşullanma
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2020
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Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
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info:eu-repo/semantics/openAccess
Özet
Bu çalışmanın amacı, kısa iskemik aralıklarla, tek taraflı alt ekstemiteye uygulanan uzak iskemik önkoşullamanın (UİÖK); ratlarda sepsise bağlı akut böbrek hasarı (ABH) üzerindeki etkilerini histopataolojik incelemeyle, kan ve idrar belirteçleriyle değerlendirmektir. Yöntem Ratlar altı gruba ayrıldı. Her grupta on adet Wistar Albino cinsi sıçan kullanıldı. Sepsis modelini oluşturmak için çekal ligasyon ve ponksiyon (CLP) yöntemi kullanıldı. Grup1 (Sham)'de sadece abdominal insizyon yapıldı ve CLP uygulanmadı. Grup2 ve Grup3'te CLP işlemi uygulandı ve sırasıyla 24. Saatte ve 48.saatte işlem sonlandırıldı. Grup 4'te UİÖK uygulandı, CLP uygulanmadı. Grup 5 ve 6'da CLP işlemi öncesinde UİÖK uygulandı ve sırasıyla 24. ve 48. Saatte işlem sonlandırıldı. Kan, idrar ve doku örnekleri alınarak prosedür sonunda ratlar sakrifiye edildi. Bütün girişimsel işlemler anestezi altında ratların spontan solunumları korunarak gerçekleştirildi. Sonuçların ilaca bağlı böbrek hasarı ile karışmaması için hayvanlara antibiyotik tedavisi uygulanmadı. Kan örneklerinden kreatinin ve laktat değerleri çalışıldı. IGFBP-7 (Insulin Like Growth Factor Binding Protein-7) ve TIMP-2 (Tissue İnhibitör of Metalloproteinaze-2) düzeyleri idrardan ELISA yöntemi ile ölçüldü. Histopatolojik değerlendirme bütün ratların sol böbreğinden gerçekleştirildi. Bulgular Böbrek histomorfolojik hasar toplam skoru Sham grubunda, diğer gruplara göre anlamlı olarak düşük bulundu (p<0,01). Tübüler Hasar Skoru sham grubuna göre sepsisin 24. ve 48. Saatinde (Grup2 ve 3'te) istatistiksel olarak anlamlı derecede artmıştır ve en fazla hasar skoru Grup3'te (sepsisin 48.saati grubunda) görülmüştür. UİÖK uygulanan ratlarla uygulanmmayanların kıyaslamasında da sepsis sonrası 24. saat ve 48.saat gruplarında; UİÖK yapılanlarda (Grup5 ve 6'da) tübüler hasarın azalması ileri derecede anlamlı şekilde bulunmuştur (p<0,001), apoptozisin azalması da anlamlı bulunmuştur (p<0,05). İdrar numunesinden ölçülen hücre siklus arrest biyobelirteçleri, hem IGFBP-7 hem de TIMP-2 sepsis sonrası 24.saat ve 48. Saat gruplarında (Grup2 ve 3 'te); sham grubuna ve birbirlerine göre anlamlı artış gösterdi. (p<0.05). Ayrıca sepsis sonrası 24. ve 48. saatlerde; işlem öncesi UİÖK yapılan gruplarda (Grup5 ve 6'da), yapılmayanlara göre IGFBP7*TIMP2 değerlerinde anlamlı azalma görülmüş (p<0.05), kreatinin ve laktat değerlerindeki değişim anlamsız bulunmuştur. (p>0,05) Sonuç Yapmış olduğumuz bu deneysel hayvan çalışmasında UİÖK'nın, sepsise bağlı akut böbrek hasarında tübüler hasarı ve apoptozisi azaltarak böbrekleri koruduğu sonucuna vardık.
The aim of this study is to evaluate the effects of remote ischemic preconditioning (RIPC) by brief ischemia of unilateral hind limb on sepsis induced acute kidney injury (SI-AKI) by histopathology, blood and urinary markers in rats. Method Rats were divided into six groups. Ten Wistar Albino rats were used in each group. The cecal ligation and puncture (CLP) method was used to create sepsis model. In Group 1 (the sham group), only abdominal incision was performed and CLP was not applied. Group 2 and Group 3 underwent CLP, and the procedure was terminated at 24.hours in Group 2 and 48. hours in Group 3. In Group 4 only RIPC and abdominal incision were applied, CLP wasn't. Group 5 and 6 underwent CLP immediately prior to the application of RIPC and procedure was terminated at 24.hours and 48.hours, respectively. Blood, urine and tissue samples were collected and rats were sacrificed at the end of the procedure. Serum creatinin and lactate levels were measured from blood. IGFBP-7 (Insulin Like Growth Factor Binding Protein-7) and TIMP-2 (Tissue Inhibitor of Metalloproteinaze-2) levels were measured by urine ELISA. Histopathological examinations were performed from the left kidney of all rats. Results The total score of kidney histomorphological damage was significantly lower in the Sham group compared to the other groups (p <0.01). The Tubular Damage Score increased significantly in the 24th and 48th hour of sepsis (in Group 2 and Group 3) compared to the sham group, and the highest damage score was seen in Group3. In comparison of the rats applied with RIPC and those not applied; in the 24th hour and 48th hour groups after sepsis (Group 5 and group6); decrease in tubular damage was found to be highly significant in rats with RIPC applied (in Group5 and 6) (p<0.001), and also decrease in apoptosis was significant (p <0.05). Cell cycle arrest biomarkers measured from the urine sample (both IGFBP-7 and TIMP-2), showed a significant increase in the 24th hour and 48th hour groups after sepsis (in Group 2 and Group 3) compared to the vii Sham group and each other. In addition, at the 24th and 48th hours after sepsis; There was a significant decrease in IGFBP7 * TIMP2 in the groups with RIPC before the procedure ( Group 5 and Group 6) compared to to those which were not applied (Group 2 and group 3) (p <0.05) Creatinine and lactate values did not change significantly. (p> 0.05) Conclusion In this experimental animal study, we concluded that RIPC protects the kidney by reducing tubular damage and apoptosis in sepsis induced acute kidney injury.
The aim of this study is to evaluate the effects of remote ischemic preconditioning (RIPC) by brief ischemia of unilateral hind limb on sepsis induced acute kidney injury (SI-AKI) by histopathology, blood and urinary markers in rats. Method Rats were divided into six groups. Ten Wistar Albino rats were used in each group. The cecal ligation and puncture (CLP) method was used to create sepsis model. In Group 1 (the sham group), only abdominal incision was performed and CLP was not applied. Group 2 and Group 3 underwent CLP, and the procedure was terminated at 24.hours in Group 2 and 48. hours in Group 3. In Group 4 only RIPC and abdominal incision were applied, CLP wasn't. Group 5 and 6 underwent CLP immediately prior to the application of RIPC and procedure was terminated at 24.hours and 48.hours, respectively. Blood, urine and tissue samples were collected and rats were sacrificed at the end of the procedure. Serum creatinin and lactate levels were measured from blood. IGFBP-7 (Insulin Like Growth Factor Binding Protein-7) and TIMP-2 (Tissue Inhibitor of Metalloproteinaze-2) levels were measured by urine ELISA. Histopathological examinations were performed from the left kidney of all rats. Results The total score of kidney histomorphological damage was significantly lower in the Sham group compared to the other groups (p <0.01). The Tubular Damage Score increased significantly in the 24th and 48th hour of sepsis (in Group 2 and Group 3) compared to the sham group, and the highest damage score was seen in Group3. In comparison of the rats applied with RIPC and those not applied; in the 24th hour and 48th hour groups after sepsis (Group 5 and group6); decrease in tubular damage was found to be highly significant in rats with RIPC applied (in Group5 and 6) (p<0.001), and also decrease in apoptosis was significant (p <0.05). Cell cycle arrest biomarkers measured from the urine sample (both IGFBP-7 and TIMP-2), showed a significant increase in the 24th hour and 48th hour groups after sepsis (in Group 2 and Group 3) compared to the vii Sham group and each other. In addition, at the 24th and 48th hours after sepsis; There was a significant decrease in IGFBP7 * TIMP2 in the groups with RIPC before the procedure ( Group 5 and Group 6) compared to to those which were not applied (Group 2 and group 3) (p <0.05) Creatinine and lactate values did not change significantly. (p> 0.05) Conclusion In this experimental animal study, we concluded that RIPC protects the kidney by reducing tubular damage and apoptosis in sepsis induced acute kidney injury.
Açıklama
Anahtar Kelimeler
Uzak İskemik Önkoşullanma, Sepsis, Akut Böbrek Hasarı, Hücre Siklus Arrest Biyobelirteçler, Remote ischemic preconditioning, Sepsis, Acute kidney injury, Cell cycle arrest biomarkers
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Künye
Cihan, E. F. (2020). Ratlarda sepsise bağlı akut böbrek hasarının önlenmesindeuzak iskemik önkoşullanma. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Cerrahi Tıp Bilimleri Bölümü Anesteziyoloji ve Reanimasyon Anabilim Dalı, Konya.
