Elastase modifies bleomycin-induced pulmonary fibrosis in mice

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• 作者：Larissa Alexsandra Silva Neto Trajano^a ; Eduardo Tavares Lima Trajano^a ; Manuella Lanzetti^b ; Morena Scopel Amorim Mendonç ; a^c ; Rafael Freitas Guilherme^c ; Rodrigo Tinoco Figueiredo^c ; Clá ; udia Farias Benjamim^c ; Samuel Santos Valenca^b ; ^{samuelv@ufrj.br" class="auth_mail" title="E-mail the corresponding author} ; André ; a Monte Alto Costa^a ; Luí ; s Crist&oacute ; vã ; o Porto^a
• 关键词：Pulmonary fibrosis ; Emphysema ; Elastase ; Bleomycin
• 刊名：Acta Histochemica
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：118
• 期：3
• 页码：203-212
• 全文大小：6674 K

文摘

Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1 U/mouse); elastase (using porcine pancreatic elastase (PPE) + bleomycin (3 U/mouse 14 days before 0.1 U/mouse of bleomycin; PPE + B); elastase (3 U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE + B group. In the PPE + B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE + B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase (p < 0.05), catalase (p < 0.01) and glutathione peroxidase (p < 0.01) parallel with an increase in nitrite (p < 0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced (p < 0.05, p < 0.05 and p < 0.01, respectively) and increased (p < 0.01) in the PPE + B group at 21 days compared with the control group. Interleukin (IL)-1β expression was upregulated (p < 0.01) whereas IL-6 was downregulated (p < 0.05) in the PPE + B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group.