The therapeutic efficacy of Ulinastatin for rats with smoking inhalation injury.
Smoke inhalation injury represents a major cause of mortality in burn patients and is associated with a high incidence of pulmonary complications. Ulinastatin (UTI) has been widely used as a drug for patients with severe burn, sepsis, severe acute pancreatitis, and multiple organ dysfunction syndrome. In view of the critical role of inflammatory response in pathogenesis of smoke inhalation-induced lung injury and the anti-inflammatory effects of UTI, we hypothesized that treatment with UTI could lessen smoke inhalation-induced lung injury. In this study, fifty-four rats were equally randomized to three groups: Sham group (ambient air inhalation), Control group (smoke inhalation injury) and UTI treatment group (UTI treatment plus smoke inhalation injury). At sampling, bronchoalveolar lavage fluid was performed to determine total protein concentration and pro-inflammatory cytokine levels. Lung tissues were collected for the measurement of wet/dry ratio, myeloperoxidase, histopathology, hydroxyproline, collagens I and III, and western blotting. Our present work exhibited that UTI attenuated the lung histopathological alterations, improved the pulmonary function, inhibited neutrophil accumulation and mitigated pulmonary edema. In addition, UTI mitigated the inflammatory response, and further prevented the initiation of downstream inflammatory cascades: NF-κB and p-JNK. Importantly, UTI also mitigated smoke inhalation-induced pulmonary fibrosis as evidenced by Masson-Goldner trichrome staining with the content of hydroxyproline and collagens I and III. In conclusion, our data demonstrated that UTI protected rat against smoke inhalation-induced acute lung injury and the subsequent development of pulmonary fibrosis.
Department of Burns & Plastic Surgery, 309th Hospital of PLA, Beijing, China.
Xiaochen
X
Qiu
Shizhao
S
Ji
Junjie
J
Wang
Hengyu
H
Li
Ting
T
Xia
Bohan
B
Pan
Shichu
S
Xiao
Zhaofan
Z
Xia
D055371:Acute Lung Injury / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015208:Smoke Inhalation Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D000893:Anti-Inflammatory Agents; D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D006023:Glycoproteins; C028665:urinastatin; D006909:Hydroxyproline