İsmail CİNEL, Şebnem ATICI, Leyla CİNEL, Zeliha KOÇAK, Ali ALTUNKAN, Lülüfer TAMER, Uğur ORAL

Endotoksinin indüklediği diyafragma fonksiyon bozukluğunda poli (ADP-Riboz) sentaz inhibisyonunun rolü

Çalışmamızda LPS ile indüklenen deneysel sepsis modelinde poli (ADP-Riboz) sentaz (PARS) inhibitörü kullanımının diyafragma Ca++-ATPaz ve malondialdehit (MDA) düzeyleri ile histopatoloji üzerine etkisi araştırıldı. Erkek Wistar ratlarda 4 grup (n=6) olarak gerçekleştirilen bu çalışmada sırası ile serum fizyolojik, lipopolisakkarit (LPS serotip L-2880, Sigma), 3-Aminobenzamid (PARS inhibitörü, Sigma) ve LPS'den 20 dk. önce verilen 3-Aminobenzamid kullanıldı. Intraperitoneal olarak verilen LPS ve 3-AB 10 mg/kg dozda kullanıldı. Denekler 6. saatin sonunda Ketamin/Xylasin anestezisi uygulanarak dekapite edildi ve diyafragma biyokimyasal çalışma ve histopatolojik, inceleme için çıkarıldı. Hematoksilen-Eozin ile boyanan kesitlerde kas histopalolojisi değerlendirildi. Ca.++-ATPaz ölçümünde inkübasyon ortamı Reading-Ispir, inorganik fosfat ölçümü Ames-Dubin ve spesifik aktivite ölçümünde kullanılan protein miktarı Lowry yöntemine göre çalışıldı. Doku MDA. düzeylerinin değerlendirilmesinde ise Hiroshi ve ark. 'nın önerdiği yöntem kullanıldı. Sepsisle diyafragma. Ca++-ATPaz düzeylerinin (548+14 v.s 215+22 nmolPi/mg protein/saat) azaldığı, MDA düzeylerinin (4.2±0.1 vs 11.7+0.4) arttığı saptandı (p=0.01). 3 AB + Sepsis grubunda her iki parametrede de kontrol grubu ile farklılık yoktu (p=0.01). Histopatolojik değerlendirmede ise minimal ödem dışında gruplararası fark saptanmadı. Myoflament fonksiyonunu gösteren Ca++-ATPaz aktivitesindeki azalmanın ve serbest radikal hasarının PARS inhibisyonu ile önlenmesi sepsiste peroksinitrit-PARS yolağının rolüne işaret etmektedir.

The role of poly (ADP ribose) synthetase inhibition in endotoxin-induced diaphragmatic dysfunction

In our experimental study, effects of poly (ADP-ribose) synthetase (PARS inhibition on diaphragm Ca++-ATPase, malondialdehyde (MDA) levels and histopathology in LPS-induced sepsis are investigated. 24 male Wistar rats, weighing 180-200 g were randomly divided into 4 groups. The first group (control; n=6) received saline and II. group (sepsis; n=6) received 10mg/kg LPS intraperitoneally. As a PARS inhibitor; 3-Aininobenzamide (3-AB) was given to the IV. group (S+3-AB, n=6) 20 minutes before giving LPS and to the III. group (C+ 3-AB, n=6) 20 minutes before giving saline. Six hours later, under Ketamin/Xylasine. anaesthesia diapraghmatic specimens were obtained and the rats were decapitated. Tissue MDA levels and Ca++-ATPase activity were measured and diaphragmatic specimens were stained with hematoxylin-eosin for histopathologic assessment. Tissue Ca++-ATPase levels were found to be decreased (548±14 vs 215+22 nmol/Pi/mg.protein/hr and tissue MDA levels were found to be increased (4.2+0.1 us 11.7±0.4) in endotoxemic group (p=0.01). In the S+ 3-AB group, 3-AB pretreatment attenuated the increase in MDA formation and Ca.++-ATPase levels were similar to those in control group (p=0.01). Except minimal edema, no difference, was seen in diaphragm histopathology among the groups. PARS inhibition with 3-AB prevents not only lipid peroxidation but also biochemical changes concerning Ca++-ATPase in endotoxemia.

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