Sıçanlarda çekal bağlama ve delme yöntemi ile oluşturulan deneysel sepsis modelinde CDP-kolinin karaciğer ve ince bağırsak hasarı üzerindeki koruyucu etkilerinin morfolojik açıdan araştırılması
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Date
2019-06-14
Authors
Tihan, Necdet Deniz
Journal Title
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Publisher
Bursa Uludağ Üniversitesi
Abstract
Amaç: Sepsisin yoğun bakım ünitelerindeki hastalar arasında insidansı %37’dir ve yüksek mortalite oranlarıyla seyretmektedir. CDP-kolin, fosfatidilkolin sentezinde ara ürün olarak sentezlenen mononükleotid yapıda bir moleküldür. Literatürde, CDP-kolin’in eksojen olarak verildiğinde hücre membran fonksiyonlarını olumlu etkilediğini gösteren çalışmalar vardır. Çalışmada, intraperitoneal sepsiste karaciğer ve ince bağırsakta gelişen morfolojik olumsuz değişiklikler üzerine CDP-kolin’in etkisinin araştırılması amaçlanmaktadır. Gereç ve Yöntem: Deneylerde 50 adet erkek Wistar albino sıçan kullanıldı. Hayvanlar 5 gruba ayrıldılar. Grup 1: sham grubu; Grup 2: kontrol grubu; Grup 3: 100 mg/kg CDP-kolin uygulanan grup; Grup 4: 200 mg/kg CDP-kolin uygulanan grup ve Grup 5: sepsis grubu. Sepsis modeli, sıçanların çekumlarının bağlanması ve delinmesi yöntemiyle oluşturuldu. Deney hayvanlarının nabız dakika sayısı (NDS), ortalama arter basıncı (OAB) ve rektal ısı (RI) parametreleri takip edildi. Aynı zamanda karaciğer ve ince bağırsak dokuları hem histolojik olarak hem de hasarın derecelendirilmesi açısından sayısal ve niteliksel olarak incelendi. Bulgular: Analizlerde, başlangıç NDS ile 4. ve 8. saatte bakılan NDS arasında yüzde değişim (YD) açısından tüm gruplarla sepsis grubu (grup 5) arasında anlamlı fark saptandı (p<0.05). Ayrıca başlangıç OAB ile 4. ve 8. saatteki OAB arasında YD açısından tüm gruplarla sepsis grubu arasında anlamlı fark saptandı (p<0.001). Sekizinci saatteki OAB değerlerinde ayrıca sham grubuyla CDP-kolin verilen gruplar arasında da YD açısından fark saptandı (p=0.008 ve p=0.028). Dördüncü saatteki RI YD açısından sham grubuyla sepsis grubu, kontrol grubuyla sepsis grubu ve 200 mg CDP-kolin grubuyla sepsis grubu arasında fark saptandı (sırasıyla p=0.002, p<0.001, p=0.004). Sekizinci saatteki YD açısından sham grubuyla 100 mg CDP-kolin grubu, sham grubuyla sepsis grubu, kontrol grubuyla 100 mg CDP-kolin grubu ve kontrol grubuyla sepsis grubu arasında fark saptandı (sırasıyla p=0.007, p<0.001, p=0.048 ve p<0.001). Doku örneklerinde karaciğer hasarı değerlendirildiğinde, gruplar arasında istatistiksel açıdan anlamlılık saptandı (p<0.001). Grup 5 ile CDP-kolin grupları karşılaştırıldığında, tüm parametreler açısından gruplar arasında farklılık saptandı (p<0.001). İnce bağırsak hasarı değerlendirildiğinde, gruplar arasında istatistiksel anlamlılık saptandı (p<0.001). Grup 5 ile her iki CDP-kolin grubu karşılaştırıldığında, parametreler açısından gruplar arasında farklılık saptandı (p<0.001). İnce bağırsak hasar parametreleri açısından CDP-kolin doz grupları arasında istatistiksel açıdan anlamlı farklılık saptanmadı (p>0.999). Sepsis grubunda doku örneklerinde hücresel ölüme rastlanırken CDP-kolin dozunun daha yüksek uygulandığı grup 4’ten alınan dokularda hücre ölümüne rastlanmadı. Sonuç: Deneysel sepsis modelinde CDP-kolin tedavisinin sepsisin ve septik şokun klinik parametrelerini kısmen düzelttiği, hepatositlerde ve enterositlerde sepsise bağlı oluşan mikroanatomik hasarları geri çevirebildiği ve belli dozların üzerinde verilen sitikolinin endotoksemiye bağlı hücre ölümünü engellediği görüldü.
Objective: Sepsis has a very high mortality rate among the intensive care unit patients and its incidence may rise up to 37%. CDP-choline which has mononucleotide structure, is an endogenous borderline product during the phosphatidylcholine synthezis from cellular membrane phospholipides. In literature, there are some researches manifesting the positive effects of exogenous CDP-choline on cellular membrane fonctions. Thus, in the study, we aim to examine the cytological and molecular mechanism of CDP-choline’s effect on morphological damages of intestine and liver tissue due to intraperitoneal sepsis. Material and Method: During the experiments, 50 male Wistar albino rats were used. They divided into 5 groups. Group 1: sham group; Group 2: kontrol group; Group 3: 100 mg/kg CDP-choline group and Group 4: 200 mg/kg CDPcholine group and Group 5: sepsis group. Sepsis model was conducted by cecal ligation and puncture method. Vital parameters of animal subjects – such as pulse, mean arterial pressure and rectal heat – were documented. Also, qualitative and quantitative investigation of scale of cytologic damage of hepatic and intestinal tissue were performed. Results: Data analysis revealed that there was a significant difference between the initial pulse per minute and pulses per minute in the 4th and 8th hours in terms of percentage change between all groups and the sepsis group (group 5) (p <0.05). In addition, there was a significant difference between the initial mean arterial pressure and the mean arterial pressure at the 4th and 8th hours in terms of percentage change between all groups and the sepsis group (p <0.001). The mean arterial pressure values at the eighth hour were also different between the sham group and the CDP-choline group (p = 0.008 and p = 0.028). In the fourth hour, there was a difference between the sham group and the sepsis group, the control group and the sepsis group and the 200 mg CDP-choline group and the sepsis group (p = 0.002, p <0.001, p = 0.004, respectively). In terms of percentage change in the eighth hour, there were differences between 100 mg CDP-choline group with sham group, sepsis group with sham group, 100 mg CDP-choline group with control group and sepsis group with control group (p = 0.007, p <0.001, p = 0.048 and p <0.001). When the liver damage was evaluated in tissue samples, a statistically significant difference was found between whole groups (p <0.001). When CDP-choline groups were compared to each other, there was a significant difference between them (p <0.001). When the intestinal damage was evaluated, a statistically significant difference was found between the groups (p <0.001). When CDP-choline group was compared with group 5, there was a significant difference between the groups in terms of parameters IX (p <0.001). There was no statistically significant difference between CDP-choline dose groups in terms of small bowel damage parameters (p> 0.999). In the sepsis group, cellular death was observed in the tissue samples, but the cell death was not found in the tissues taken from group 4, where the dose of CDP-choline was higher. Conclusion: In the experimental sepsis model, CDP-choline treatment partially corrected the clinical parameters of sepsis and septic shock, and reversed microanatomic damage due to sepsis in hepatocytes and enterocytes, and citicoline given on certain doses inhibited endotoxemia-induced cell death.
Objective: Sepsis has a very high mortality rate among the intensive care unit patients and its incidence may rise up to 37%. CDP-choline which has mononucleotide structure, is an endogenous borderline product during the phosphatidylcholine synthezis from cellular membrane phospholipides. In literature, there are some researches manifesting the positive effects of exogenous CDP-choline on cellular membrane fonctions. Thus, in the study, we aim to examine the cytological and molecular mechanism of CDP-choline’s effect on morphological damages of intestine and liver tissue due to intraperitoneal sepsis. Material and Method: During the experiments, 50 male Wistar albino rats were used. They divided into 5 groups. Group 1: sham group; Group 2: kontrol group; Group 3: 100 mg/kg CDP-choline group and Group 4: 200 mg/kg CDPcholine group and Group 5: sepsis group. Sepsis model was conducted by cecal ligation and puncture method. Vital parameters of animal subjects – such as pulse, mean arterial pressure and rectal heat – were documented. Also, qualitative and quantitative investigation of scale of cytologic damage of hepatic and intestinal tissue were performed. Results: Data analysis revealed that there was a significant difference between the initial pulse per minute and pulses per minute in the 4th and 8th hours in terms of percentage change between all groups and the sepsis group (group 5) (p <0.05). In addition, there was a significant difference between the initial mean arterial pressure and the mean arterial pressure at the 4th and 8th hours in terms of percentage change between all groups and the sepsis group (p <0.001). The mean arterial pressure values at the eighth hour were also different between the sham group and the CDP-choline group (p = 0.008 and p = 0.028). In the fourth hour, there was a difference between the sham group and the sepsis group, the control group and the sepsis group and the 200 mg CDP-choline group and the sepsis group (p = 0.002, p <0.001, p = 0.004, respectively). In terms of percentage change in the eighth hour, there were differences between 100 mg CDP-choline group with sham group, sepsis group with sham group, 100 mg CDP-choline group with control group and sepsis group with control group (p = 0.007, p <0.001, p = 0.048 and p <0.001). When the liver damage was evaluated in tissue samples, a statistically significant difference was found between whole groups (p <0.001). When CDP-choline groups were compared to each other, there was a significant difference between them (p <0.001). When the intestinal damage was evaluated, a statistically significant difference was found between the groups (p <0.001). When CDP-choline group was compared with group 5, there was a significant difference between the groups in terms of parameters IX (p <0.001). There was no statistically significant difference between CDP-choline dose groups in terms of small bowel damage parameters (p> 0.999). In the sepsis group, cellular death was observed in the tissue samples, but the cell death was not found in the tissues taken from group 4, where the dose of CDP-choline was higher. Conclusion: In the experimental sepsis model, CDP-choline treatment partially corrected the clinical parameters of sepsis and septic shock, and reversed microanatomic damage due to sepsis in hepatocytes and enterocytes, and citicoline given on certain doses inhibited endotoxemia-induced cell death.
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Keywords
CDP-kolin, CDP-choline, Sepsis, Enfeksiyon, Enflamasyon, Hücre hasarı, Sepsis, Infection, Inflammation, Cell damage
Citation
Tihan, N. D. (2019). Sıçanlarda çekal bağlama ve delme yöntemi ile oluşturulan deneysel sepsis modelinde CDP-kolinin karaciğer ve ince bağırsak hasarı üzerindeki koruyucu etkilerinin morfolojik açıdan araştırılması. Yayınlanmamış doktora tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.