Ratlarda bleomisin ile indüklenmiş akciğer fibrozisine tofacitinib etkisinin değerlendirilmesi
Küçük Resim Yok
Tarih
2022
Yazarlar
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Yayıncı
T.C. Maltepe Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç : Romatolojik hastalıklarla ilişkili olarak meydana gelen ve hayat kalitesini etkileyen en ciddi patolojilerden birisi interstisyel akciğer hastalığıdır. İnterstisyel akciğer hastalığı romatolojik hastalıklara bağlı olarak hastalığın evresine , mevcut tedaviye bağlı olarak farklı histolojik paternler içerebilir. Akciğer fibrozisi gelişmiş İAH lı olgularda romatolojik hastalık gelişme oranları cinsiyetler arasında anlamlı farklılık göstermemektedir. Ancak romatolojik hastalığa sekonder İAH gelişiminin cinsiyetlere göre dağılımında farklar mevcuttur. Romatolojik hastalığı olan erkeklerde İAH gelişme riski kadınlara oranla üç kat daha fazladır. RA, SSc gibi hastalıklarda en sık tutulum gösteren ekstra artiküler organ akciğerdir. Altta yatan hastalığın neden olduğu immünolojik hadiseler akciğerde hasara neden olur ve bu olaylar İAH için genel olarak başlangıç teşkil eder. Mevcut DMARD ajanların İAH gelişimini önlemesi üzerine net veriler elde edilebilmiş değildir. Ancak son dönemde Janus-Kinaz (JAK) inhibitörlerinin akciğerde meydana gelene interstisyel hasarları önleyebildiği yönünde yayınlar mevcuttur. Bu konuda net bir patofizyolojik mekanizmasının ortaya konulması ve tedavi algoritması geliştirilmesi hastalığın kontrol ve yönetimi kolaylaştırabilecektir. Gereç ve Yöntem: Maltepe Üniversitesi Deney Hayvanları Uygulama ve Araştırma Merkezi (MÜDEHAM)’da daha önceden yetiştirilen yaklaşık 200-250 gr ağırlığında, erkek , 27 adet Spraque-Dawley albino rat çalışmada kullanıldı. Ratlar genel anestezi altında intrakardiyak kan alma tekniği ile sakrifiye edildi. Maltepe Üniversitesi Tıp Fakültesi Hastanesi Patoloji laboratuvarında ve Memorial Patoloji Laboratuvarında örneklerin akciğer dokuları patolojik olarak incelendi ve İmageJ programı ile bağ doku alanları ve oranları belirlendi. Maltepe Üniversitesi Kanser ve Kök Hücre Araştırma Merkezi’nde deneklerden alınan kan örneklerinde IL-6, IL-10,IL-13, IL-17, KL-6 düzeyleri ölçüldü. İstatiksel Analiz: Çalışma kapsamında toplanan veriler IBM Sosyal Bilimler için veri analizi programı paket versiyon 23.0 ile analiz edildi. Sürekli veriler için ortalama, standart sapma, medyan, minimum ve maksimum tanımlayıcı değer olarak verildi. Normallik varsayımı Shapiro-Wilk testi ile değerlendirildi. Gruplar arası karşılaştırmalarda, “ANOVA Testi”, gruplar arasında anlamlı farklılığın hangi gruptan kaynaklandığını belirlemek için Post-Hoc “Bonferroni Testi” kullanıldı. Ölçüm değerleri arasındaki ilişkiler “Pearson Korelasyon Testi” ile değerlendirildi. Sonuçlar, p değerinin 0,05’ten küçük olduğu durumlarda istatistiksel olarak anlamlı kabul edildi. Bulgular : Çalışmaya 23 adet erkek cinsiyette Wistar Albino rat alındı. Kontrol grubu dışındaki gruplarda bleomisin aracılığı ile fibrozis gelişimi sağlandı. A1 ve A2 grupları tofasitinib ile tedavi edildi. Bağ dokusu alanı ve bağ dokusu oranı ölçümlerinde gruplar arasında istatistiksel açıdan anlamlı farklılık bulunmuştur . Çalışma kapsamındaki deneklerin KL-6 ölçümleri ile interlökin ölçümleri arasında istatistiksel açıdan anlamlı bir ilişki olmadığı belirlenmiştir (p>0,05). Toplam doku alanı dağılımları A1 grubunun en yüksek, A2 grubunun ise en düşük olduğu görülmektedir. Deney gruplarının interlökin-6 ölçümleri A1 grubunun en düşük olduğu görüldü. İnterlökin-10 ölçümleri A2 grubunun interlökin-10 ölçümlerinin en yüksek, A1 grubunun ise en düşük olduğu görüldü. İnterlökin-13 ölçümlerinin en yüksek, kontrol grubunun ise en düşük ölçüldü. İnterlökin-17 ölçümlerinin en yüksek A2 grubunda ölçüldü. A1 grubunun KL-6 seviyesi en yüksek saptandı. Tartışma ve Sonuç: Tofasitinib profilaktik olarak uygulanan denekler de bağ doku gelişimi daha az saptanmıştır. Ayrıca yine bu grupta proinflamatuar sitokin IL-6 seviyesi düşük saptanmıştır. Kontra inflamatuar bir sitokin olan IL-10 seviyeleri de daha yüksek ölçüldü. Tofasitinib in romatolojik hastalıklarda meydana gelen interstisyel akciğer hastalığı gelişiminde koruyucu etkisi olabileceği düşünüldü. Sonuç olarak tofasitinib romatolojik hastalıklarda hastalıklara bağlı artiküler semptomlarla birlikte interstisyel hasara yönelik koruyucu olabilir. Mevcut bulgular daha büyük çalışmalarla da desteklenmelidir.
Aim: Interstitial lung disease is one of the most serious pathologies associated with rheumatic diseases and affecting quality of life. Interstitial lung disease may have different histological patterns depending on the stage of the disease, the treatment available, depending on the rheumatological diseases. The rates of rheumatologic disease development in ILD patients with lung fibrosis do not differ significantly between genders. However, there are differences in the distribution of the development of ILD secondary to rheumatologic disease by gender. Men with rheumatic diseases are three times more likely to develop ILD than women. The most frequently involved extra-articular organ in diseases such as RA and SSc is the lung. Immunological events caused by the underlying disease cause lung damage and these events are generally the beginning of ILD. There are no clear data on the current DMARD agents preventing the development of ILD. However, there are recent reports that Janus-Kinase (JAK) inhibitors can prevent interstitial damage to the lung. In this regard, revealing a clear pathophysiological mechanism and developing a treatment algorithm will facilitate the control and management of the disease. Material and Method: Twenty-three male Spraque-Dawley albino rats, weighing approximately 200-250 g, previously bred in Maltepe University Experimental Animals Application and Research Center (MÜDEHAM) were used in the study. Rats were sacrificed by intracardiac blood collection technique under general anesthesia. Lung tissues of the samples were pathologically examined in the Pathology laboratory of Maltepe University Medical Faculty Hospital and Memorial Pathology Laboratory, and connective tissue areas and ratios were determined with the ImageJ program. IL-6, IL-10, IL-13, IL-17, KL-6 levels were measured in blood samples taken from the subjects at Maltepe University Cancer and Stem Cell Research Center. Statistical Analysis: The data collected within the scope of the study were analyzed with the IBM data analysis program package version 23.0 for Social Sciences. For continuous data, mean, standard deviation, median, minimum and maximum descriptive values were given. Normality assumption was evaluated with the Shapiro-Wilk test. In comparisons between groups, the "ANOVA Test" was used, and the Post-Hoc "Bonferroni Test" was used to determine which group caused the significant difference between the groups. The relationships between the measurement values were evaluated with the “Pearson Correlation Test”. The results were considered statistically significant when the p value was less than 0,05. Result: Twenty-three male Wistar Albino rats were included in the study. Fibrosis development was achieved by means of bleomycin in groups other than the control group. Groups A1 and A2 were treated with tofacitinib. A statistically significant difference was found between the groups in the measurements of connective tissue area and connective tissue ratio. It was determined that there was no statistically significant relationship between KL-6 measurements and interleukin measurements of the subjects within the scope of the study (p>0.05). It is seen that the total tissue area distributions are the highest in the A1 group and the lowest in the A2 group. Interleukin-6 measurements of the experimental groups were the lowest in the A1 group. Interleukin-10 measurements It was seen that the interleukin-10 measurements of the A2 group were the highest, while the A1 group was the lowest. Interleukin-13 measurements were the highest and the control group had the lowest. Interleukin-17 measurements were highest in the A2 group. The KL-6 level of the A1 group was the highest. Conclusion: Connective tissue development was found to be less in subjects treated with tofacitinib prophylactically. In addition, the proinflammatory cytokine IL-6 level was found to be low in this group. Levels of IL-10, a contra-inflammatory cytokine, were also measured higher. It was thought that tofacitinib may have a protective effect on the development of interstitial lung disease in rheumatological diseases. In conclusion, tofacitinib may be protective against interstitial damage in rheumatologic diseases with disease-related articular symptoms. Existing findings should also be supported by larger studies.
Aim: Interstitial lung disease is one of the most serious pathologies associated with rheumatic diseases and affecting quality of life. Interstitial lung disease may have different histological patterns depending on the stage of the disease, the treatment available, depending on the rheumatological diseases. The rates of rheumatologic disease development in ILD patients with lung fibrosis do not differ significantly between genders. However, there are differences in the distribution of the development of ILD secondary to rheumatologic disease by gender. Men with rheumatic diseases are three times more likely to develop ILD than women. The most frequently involved extra-articular organ in diseases such as RA and SSc is the lung. Immunological events caused by the underlying disease cause lung damage and these events are generally the beginning of ILD. There are no clear data on the current DMARD agents preventing the development of ILD. However, there are recent reports that Janus-Kinase (JAK) inhibitors can prevent interstitial damage to the lung. In this regard, revealing a clear pathophysiological mechanism and developing a treatment algorithm will facilitate the control and management of the disease. Material and Method: Twenty-three male Spraque-Dawley albino rats, weighing approximately 200-250 g, previously bred in Maltepe University Experimental Animals Application and Research Center (MÜDEHAM) were used in the study. Rats were sacrificed by intracardiac blood collection technique under general anesthesia. Lung tissues of the samples were pathologically examined in the Pathology laboratory of Maltepe University Medical Faculty Hospital and Memorial Pathology Laboratory, and connective tissue areas and ratios were determined with the ImageJ program. IL-6, IL-10, IL-13, IL-17, KL-6 levels were measured in blood samples taken from the subjects at Maltepe University Cancer and Stem Cell Research Center. Statistical Analysis: The data collected within the scope of the study were analyzed with the IBM data analysis program package version 23.0 for Social Sciences. For continuous data, mean, standard deviation, median, minimum and maximum descriptive values were given. Normality assumption was evaluated with the Shapiro-Wilk test. In comparisons between groups, the "ANOVA Test" was used, and the Post-Hoc "Bonferroni Test" was used to determine which group caused the significant difference between the groups. The relationships between the measurement values were evaluated with the “Pearson Correlation Test”. The results were considered statistically significant when the p value was less than 0,05. Result: Twenty-three male Wistar Albino rats were included in the study. Fibrosis development was achieved by means of bleomycin in groups other than the control group. Groups A1 and A2 were treated with tofacitinib. A statistically significant difference was found between the groups in the measurements of connective tissue area and connective tissue ratio. It was determined that there was no statistically significant relationship between KL-6 measurements and interleukin measurements of the subjects within the scope of the study (p>0.05). It is seen that the total tissue area distributions are the highest in the A1 group and the lowest in the A2 group. Interleukin-6 measurements of the experimental groups were the lowest in the A1 group. Interleukin-10 measurements It was seen that the interleukin-10 measurements of the A2 group were the highest, while the A1 group was the lowest. Interleukin-13 measurements were the highest and the control group had the lowest. Interleukin-17 measurements were highest in the A2 group. The KL-6 level of the A1 group was the highest. Conclusion: Connective tissue development was found to be less in subjects treated with tofacitinib prophylactically. In addition, the proinflammatory cytokine IL-6 level was found to be low in this group. Levels of IL-10, a contra-inflammatory cytokine, were also measured higher. It was thought that tofacitinib may have a protective effect on the development of interstitial lung disease in rheumatological diseases. In conclusion, tofacitinib may be protective against interstitial damage in rheumatologic diseases with disease-related articular symptoms. Existing findings should also be supported by larger studies.
Açıklama
Anahtar Kelimeler
İnterstisyel akciğer hastalığı, Tofasitinib, JAK/STAT, Romatoid artrit, Sistemik skleroderma, Interstitial lung disease, Tofacitinib, JAK/STAT, Rheumatoid arthritis, Systemic scleroderma
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Soylu, İ. (2022). Ratlarda bleomisin ile indüklenmiş akciğer fibrozisine tofacitinib etkisinin değerlendirilmesi / Evaluation of the effect of tofacitinib on bleomycin-induced lung fibrosis in rats.(Yayımlanmamış Tıpta Uzmanlık Tezi). Maltepe Üniversitesi, Tıp Fakültesi Enstitüsü, İstanbul.
