CDP-kolin'in septik şok modelinde kan basıncı ve doku hasarı üzerine etkilerinin araştırılması
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Date
2014
Authors
Sevim, Çiğdem
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Publisher
Uludağ Üniversitesi
Abstract
CDP-kolin vücutta endojen olarak üretilen nükleotid yapısında bir bileşik ve kafa travması gibi bazı hastalıklarda kullanılan bir ilaçtır. Sıçanlarda farklı şok modellerinde bozulan hemodinamik parametreleri iyileştirdiği ve doku hasarını önlediği gösterilmiştir. CDP-kolin'in bu etkilerine büyük ölçüde kolinerjik sistemin aktivasyonu aracılık etmektedir. Çalışmamızda; daha önce araştırılmamış olan septik şok modelinde CDP-kolin'in, şoka bağlı gelişen hipotansiyon ve inflamasyon üzerine etkisi araştırıldı ve koruyucu etkileri değerlendirildi. Deneylerde Sprague-Dawley erkek sıçanlar kullanıldı. Sevofluran anestezisi (% 2,5-4) altında sıçanların arter (a. Carotis) ve ven (v. Jugularis) kanülasyonları yapıldı. Septik şok tablosu çekal ligasyon-insizyon yöntemiyle oluşturuldu. Bu amaçla hayvanların çekumları çıkarılarak bistüri yardımıyla 0.75 mm'lik kesi atıldı. Sham grubunda sadece çekal ligasyon yapıldı. Operasyon sonrası 10 dakikalık stabilizasyon periyodunun ardından deneysel monitorizasyona başlandı. CDP-kolin (100 mg/kg) veya tuzlu su (1ml/kg) enjeksiyonu intravenöz yolla ve deneyin 180. dakikasında yapıldı. Enjeksiyonlardan sonra 210 dakika takip edilen hayvanlardan sitokin ölçümleri için kan örnekleri (200 ul) alındı ve sevofluran anestezisi altında perfüze edilerek immünohistokimyasal incelemeler için akciğer, karaciğer, böbrek ve dalakları çıkarıldı. Çekal ligasyon-insizyon işlemi kan basıncını düşürdü ve kalp hızını artırdı. 180. dakikada enjekte edilen CDP-kolin (100 mg/kg; i.v.) hipotansiyonu hızla düzeltti ve kan basıncını ilk 60 dakikada kontrol seviyelerine yükseltti. Etki 3 saat boyunca devam etti. İlacın kalp hızına etkisi olmadı. CDP-kolin septik şoka bağlı olarak artan TNFα, IL-1b ve IL-6 düzeylerini azalttı ve akciğer, karaciğer, böbrekteki hasarı önledi. CDP-kolin'in dalak dokusundaki hasar üzerine anlamlı etkisi olmadı. Elde edilen bulgular, sıçanlarda septik şok modelinde intravenöz yolla uygulanan CDP-kolin'in kan basıncını düzelttiği, inflamasyonu azalttığı ve doku hasarını önlediğini göstermektedir.
CDP-Cholin is a medication in nucleotide structure used in head traumas. It is a compound produced in the body endogenously. It has been demonstrated that it cures the hemodynamic parameters in different shock models and prevents tissue damage in rats. Mostly, the activation of the cholinergic system acts as intermediary in these effects of the CDP-Cholin. In our study we examined the effects of the CDP-Cholin on hypotension and inflammation which develops as based on shock in septic shock models which was not previously examined in any other study. The protective effects of the CDP-Cholin has also been examined. Sprague-Dawley male rats were used in the experiments. The artery (a. Carotis) and vein (v. Jugularis) cannulations were performed under Sevoflurane anesthesia (% 2,5-4). The septic shock table was formed with the cecal ligation-incision method. For this purpose, the cecums of the animals were taken out and cut as 0.75 mm in size with the help of a bistoury. Only cecal ligation was performed in the Sham group. After the operation, we waited for 10 minutes for stabilization, and then started the experimental monitorization. CDP-Cholin (100 mg/kg) or saline (1ml/kg) injection was performed intravenously in the 180th minute of the experiment. The animals were observed for 210 minutes after the injections, and then blood samples were taken (200 ul) for cytokine measurements. These were perfused under sevoflurane anesthesia, and the livers, kidneys and spleens were taken out for immune-histo-chemical examinations. The Cecal ligation-incision process decreased the blood pressure and increased the heart beat rate. The CDP-Cholin injected in the 180th minute (100 mg/kg; i.v.) quickly recovered the hypotension, and increased the blood pressure up to control levels in the first 60 minutes. The effect lasted for 3 hours. The medication did not affect the heart beat rate. The CDP-Cholin decreased the TNFα, IL-1b and IL-6 levels which had occurred before due to the septic shock, and prevented the damage in the lungs, liver and kidneys. The CDP-Cholin did not have a meaningful effect on the damage on the spleen tissue. The findings show that the CDP-Cholin applied intravenously to the septic shock models in rats regulates the blood pressure, decreases inflammation and prevents tissue damage. Key Words: CDP-Cholin, inflammation, septic shock, cytokine, multiple organ failure.
CDP-Cholin is a medication in nucleotide structure used in head traumas. It is a compound produced in the body endogenously. It has been demonstrated that it cures the hemodynamic parameters in different shock models and prevents tissue damage in rats. Mostly, the activation of the cholinergic system acts as intermediary in these effects of the CDP-Cholin. In our study we examined the effects of the CDP-Cholin on hypotension and inflammation which develops as based on shock in septic shock models which was not previously examined in any other study. The protective effects of the CDP-Cholin has also been examined. Sprague-Dawley male rats were used in the experiments. The artery (a. Carotis) and vein (v. Jugularis) cannulations were performed under Sevoflurane anesthesia (% 2,5-4). The septic shock table was formed with the cecal ligation-incision method. For this purpose, the cecums of the animals were taken out and cut as 0.75 mm in size with the help of a bistoury. Only cecal ligation was performed in the Sham group. After the operation, we waited for 10 minutes for stabilization, and then started the experimental monitorization. CDP-Cholin (100 mg/kg) or saline (1ml/kg) injection was performed intravenously in the 180th minute of the experiment. The animals were observed for 210 minutes after the injections, and then blood samples were taken (200 ul) for cytokine measurements. These were perfused under sevoflurane anesthesia, and the livers, kidneys and spleens were taken out for immune-histo-chemical examinations. The Cecal ligation-incision process decreased the blood pressure and increased the heart beat rate. The CDP-Cholin injected in the 180th minute (100 mg/kg; i.v.) quickly recovered the hypotension, and increased the blood pressure up to control levels in the first 60 minutes. The effect lasted for 3 hours. The medication did not affect the heart beat rate. The CDP-Cholin decreased the TNFα, IL-1b and IL-6 levels which had occurred before due to the septic shock, and prevented the damage in the lungs, liver and kidneys. The CDP-Cholin did not have a meaningful effect on the damage on the spleen tissue. The findings show that the CDP-Cholin applied intravenously to the septic shock models in rats regulates the blood pressure, decreases inflammation and prevents tissue damage. Key Words: CDP-Cholin, inflammation, septic shock, cytokine, multiple organ failure.
Description
Keywords
CDP-kolin, İnflamasyon septik şok, Sitokin, Çoklu organ yetmezliği, CDP-cholin, Inflammation, Septic shock, Cytokine, Multiple organ failure
Citation
Sevim, Ç. (2014). CDP-kolin'in septik şok modelinde kan basıncı ve doku hasarı üzerine etkilerinin araştırılması. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.