Ratlarda mekanik ventilasyona bağlı olarak gelişen diyafragma atrofisinde oksidatif stresin rolü ve atrofinin önlenmesinde teofilinin etkisi
Yükleniyor...
Dosyalar
Tarih
2007
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mekanik ventilasyon uygulamasına bağlı olarak solunumun en önemli kası olan diyafragmada hareket bozukluğu ve atrofi meydana gelmektedir. Diyafragma fonksiyon bozukluğunda oksidatif stresin rolü olduğu çeşitli çalışmalar ile gösterilmiştir. Diyafragma atrofisinin önlenmesinde teofilin ve antioksidan gibi çeşitli ilaçlar kullanılmıştır. Çalışmamızda hayvan modelinde ventilasyon uygulamasına bağlı olarak diyafragma atrofisinin önlenmesinde oksidatif stresin rolünü araştırdık ve intravenöz teofilin uygulanmasının diyafragma atrofisine etkisini ve bunun önlenmesinde teofilin kullanımının gerekli olup olmadığını araştırmayı amaçladık. Çalışmamızda 30 adet, sağlıklı 4 aylık erkek Sprague-Dawley ratlar kulanıldı. Ratlar 3 gruba ayrılarak (Grup 1 MV uygulanmayan kontrol grubu, n=10; Grup 2 MV uygulanan plasebo grubu n=10; Grup 3 MV'a bağlanan ve teofilin infüzyonu uygulanan teofilin grubu n=10) çalışıldı. Her üç grupta oksidatif stresi değerlendirmek için NO, SOD, MDA, XO plazma, BL, akciğer ve diyafragmada ölçüldü. Her üç grupta atrofiyi değerlendirmek için diyafragmanın en büyük çapı ve membranöz kısmın en büyük çapı ölçüldü ve histopatolojik olarak değerlendirildi. Her üç gurubun diyafragma ağırlığı, diyafragma büyük çapı, diyafragma membranöz kısmın büyük çapı ve diyafragma ağırlığının vücut ağırlığına oranı karşılaştırıldığında diyafragma büyük çap, membranöz kısmın büyük çapı grup 2'ye göre grup 1'de daha fazlaydı. (p<0.001). Grup 3'te grup 2'ye göre daha fazlaydı. (p<0.001). Buna göre MV'nun ratların diyafragma çaplarında ve membranöz kısım büyük çaplarında azalmaya neden olduğu, teofilin uygulanmasının diyafragma ve membranöz kısımdaki çaplarda artmaya neden olduğu gösterilmiştir. Histopatolojik incelemede Grup 1'de diyafragmada makroskopik olarak kalınlaşma ve mikroskopik olarak atrofi gözlemlenmedi. Plasebo grubunda ratların tümünde makroskopik olarak belirgin kalınlaşma ve mikroskopik olarak üç pozitif atrofi gözlendi. Teofilin grubunda bir hayvanda hiç atrofi gözlenmedi. Sekiz hayvanda bir pozitif, bir hayvanda ise iki pozitif atrofi gözlendi. Bu verilere göre atrofi ve makroskopik olarak kalınlaşma açısından 3 grup arasında istatistiksel anlamlılık mevcut olup MV'nun ratların diyafragmalarında belirgin atrofiye neden olduğu ve teofilin infüzyonunun bu atrofiyi azalttığı gösterilmiştir (p<0.001, p<0.001). Diyafragma ağırlığı vücut ağırlığına oranlandığında ise grup 2 ile grup 3 arasında istatistiksel olarak anlamlılık mevcuttu (p<0.05). Grup 1 ve grup 2 arasında, plazma MDA, SOD, XO, diyafragma SOD, NO, XO açısından anlamlı farklılık mevcuttu. (p<0.05) Kontrol gurubu ile karşılaştırıldığında plasebo uygulanan gurupta MV'e bağlı olarak plazma MDA, SOD, XO ve diyafragma SOD, NO, XO açısından anlamlı artış bulundu (p<0.05 ) Grup 2 ve grup 3 arasında, plazma MDA ve XO kıyaslandığında anlamlı farklılık mevcuttu (p<0.0001, p<0.05). Serbest oksijen radikal aktivitesinin diğer bir göstergesi olan NO grup 2 ve grup 3 arasında grup 2'ye göre anlamlı olarak yüksek bulundu (p<0.01). Antioksidan aktivitenin göstergesi olan SOD sadece diyafragmadaki aktivitesi grup 3'te grup 2'ye göre anlamlı olarak artmıştı (p< 0.05). Bizim çalışmamızda MV uygulanması sonrasında ratların diyafragmasında atrofi meydana geldiği ve teofilin uygulanmasından sonra atrofinin azaldığı ve oksidatif stresin bir göstergesi olan MDA ve XO düzeylerinde plazmada azalmaya ve SOD seviyesinde artmaya dolayısıyla bir antioksidan etkiye sahip olduğu gösterilmiştir. Bunun dışında NO'de teofilin uygulanan grupta diğer gruplara göre anlamlı artış gözlendi. Bu çalışmadan daha geniş ve insan çalışmalarına ihtiyaç olduğunu düşünmekteyiz.
Movement disorder and atrophy ocur in diaphragma, the most important muscle of respiration, because of mechanical ventilation. Various studies showed that oxidative stres plays a part in diaphragma malfunction. Such drugs as theophylline and antioxidants have been used in the prevention of diaphragmatic atrophy. In our study, the significance of oxidative stres was investigated in the prevention of diaphragmatic atrophy due to ventilation on animal models and aimed at investigating the effect of intravenous theophylline administration on diaphragmatic atrophy and whether the use of theophylline is necessary in the prevention of diaphragma atrophy. In the study, healthy, 4-month-old Sprague-Dawley rats of 30 were included. The rats were studied classifying into 3 groups (Group 1, control group and not applied MV, n=10; Group 2, placebo group, applied MV, n=10, Group 3, provided with MV and theophylline administered group, n=10). In all these 3 groups, NO, SOD, MDA, XO plasma were measured in lungs and diaphragma to assess oxidative stress. In three groups, the largest diameters of the diaphragma and membranous part were measured and evaluated histopathologically. Compared the diaphragma weight, large diaphragma diameter, large diameter of diaphragma membranous part and the proportion of diaphragma weight with body weight in 3 groups, large diameter and large diameter of membranous part were found to be larger in group 1 than in group 2 (p<0.001). In group 3, it was larger, compared to group 2 (p<0.001). In light of these measurements, it was determined that MV leads to decrease in the diaphragma diameters and large diameters of membranous parts in rats, and that theophylline administration leads to increase in the diameters of diaphragma and membraneous parts. In histopathologic examination, no macroscopic thickening and microscopic atrophy were observed in diaphragma in group 1. In placebo group, macroscopically definite thickening was observed in all rats, and microscopically 3 positive atrophies were observed. In theophylline group, there was no atrophy in 1 rat. In 8 rats, a positive, and in 1 rat two positive atrophies were observed. According to these findings, there was statistically significance between 3 groups in terms of atrophy and macroscopic thickening, and it was indicated that MV leads to a marked atrophy in the diaphragma of rats and theophylline infusion decreases this atrophy (p<0.001, p<0.001). Given the proportion of diaphragma weight to body weight, a statistically significance was detected between group 2 and group 3 (p<0.05). There was a significant difference regarding MDA, SOD, XO diaphragma SOD, NO, SOD between group 1 and 2 (p<0.05). compared to control group, there was a significant increase in terms of plasma MDA, SOD, XO and diaphragma SOD, NO,XO on account of MV in placebo group (p<0.05). There was a significants difference between group 1 and group 3 when compared MDA and XO (p<0.0001, p<0.05). NO, another indicator of free oxygen radical activity, was found to be significantly higher in group 3 between group 2 and 3 (p<0.01). SOD, an indicator of antioxidant activity, was higher in group 3 than group 2 only in terms of diaphragmatic activity (p<0.05). In our study, it was indicated that atrophy occurred in the diaphragmas of rats after MV, and the atrophy was decreased after theophylline administration, and that theophylline causes a decrease in plasma at MDA and XO levels, indicators of oxidative stres, and increase at SOD level, and so it is of an antioxidant effect. In addition, a significant increase was observed in theophylline-administered group at NO level compared to other groups. We think that more detailed studies on human subject are needed.
Movement disorder and atrophy ocur in diaphragma, the most important muscle of respiration, because of mechanical ventilation. Various studies showed that oxidative stres plays a part in diaphragma malfunction. Such drugs as theophylline and antioxidants have been used in the prevention of diaphragmatic atrophy. In our study, the significance of oxidative stres was investigated in the prevention of diaphragmatic atrophy due to ventilation on animal models and aimed at investigating the effect of intravenous theophylline administration on diaphragmatic atrophy and whether the use of theophylline is necessary in the prevention of diaphragma atrophy. In the study, healthy, 4-month-old Sprague-Dawley rats of 30 were included. The rats were studied classifying into 3 groups (Group 1, control group and not applied MV, n=10; Group 2, placebo group, applied MV, n=10, Group 3, provided with MV and theophylline administered group, n=10). In all these 3 groups, NO, SOD, MDA, XO plasma were measured in lungs and diaphragma to assess oxidative stress. In three groups, the largest diameters of the diaphragma and membranous part were measured and evaluated histopathologically. Compared the diaphragma weight, large diaphragma diameter, large diameter of diaphragma membranous part and the proportion of diaphragma weight with body weight in 3 groups, large diameter and large diameter of membranous part were found to be larger in group 1 than in group 2 (p<0.001). In group 3, it was larger, compared to group 2 (p<0.001). In light of these measurements, it was determined that MV leads to decrease in the diaphragma diameters and large diameters of membranous parts in rats, and that theophylline administration leads to increase in the diameters of diaphragma and membraneous parts. In histopathologic examination, no macroscopic thickening and microscopic atrophy were observed in diaphragma in group 1. In placebo group, macroscopically definite thickening was observed in all rats, and microscopically 3 positive atrophies were observed. In theophylline group, there was no atrophy in 1 rat. In 8 rats, a positive, and in 1 rat two positive atrophies were observed. According to these findings, there was statistically significance between 3 groups in terms of atrophy and macroscopic thickening, and it was indicated that MV leads to a marked atrophy in the diaphragma of rats and theophylline infusion decreases this atrophy (p<0.001, p<0.001). Given the proportion of diaphragma weight to body weight, a statistically significance was detected between group 2 and group 3 (p<0.05). There was a significant difference regarding MDA, SOD, XO diaphragma SOD, NO, SOD between group 1 and 2 (p<0.05). compared to control group, there was a significant increase in terms of plasma MDA, SOD, XO and diaphragma SOD, NO,XO on account of MV in placebo group (p<0.05). There was a significants difference between group 1 and group 3 when compared MDA and XO (p<0.0001, p<0.05). NO, another indicator of free oxygen radical activity, was found to be significantly higher in group 3 between group 2 and 3 (p<0.01). SOD, an indicator of antioxidant activity, was higher in group 3 than group 2 only in terms of diaphragmatic activity (p<0.05). In our study, it was indicated that atrophy occurred in the diaphragmas of rats after MV, and the atrophy was decreased after theophylline administration, and that theophylline causes a decrease in plasma at MDA and XO levels, indicators of oxidative stres, and increase at SOD level, and so it is of an antioxidant effect. In addition, a significant increase was observed in theophylline-administered group at NO level compared to other groups. We think that more detailed studies on human subject are needed.
Açıklama
Anahtar Kelimeler
Mekanik Ventilasyon, Diyafragma Atrofisi, Oksidatif Stress, Teofilin, Theophylline, Oxidative Stres, Diaphragmatic Atrophy, Mechanical Ventilation
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Bakırkalay Aydın, N. (2007). Ratlarda mekanik ventilasyona bağlı olarak gelişen diyafragma atrofisinde oksidatif stresin rolü ve atrofinin önlenmesinde teofilinin etkisi. (Uzmanlık Tezi). Selçuk Üniversitesi, Tıp Fakültesi, Konya.
