Simvastatin attenuates the development of pulmonary and cutaneous fibrosis in a murine model of systemic sclerosis

被引：44

作者：

Bagnato, Gianluca ^{[1
]}

Bitto, Alessandra ^{[2
]}

Pizzino, Gabriele ^{[2
]}

Irrera, Natasha ^{[2
]}

Sangari, Donatella ^{[3
]}

Cinquegrani, Maurizio ^{[1
]}

Roberts, William Neal ^{[4
]}

Cerinic, Marco Matucci ^{[5
]}

Squadrito, Francesco ^{[2
]}

Altavilla, Domenica ^{[2
]}

Bagnato, Gianfilippo ^{[3
]}

Saitta, Antonino ^{[1
]}

机构：

[1] Univ Messina, Div Internal Med, Dept Clin & Expt Med, I-98100 Messina, Italy

[2] Univ Messina, Div Pharmacol, Dept Clin & Expt Med, I-98100 Messina, Italy

[3] Univ Messina, Div Rheumatol, I-98100 Messina, Italy

[4] Univ Louisville, Dept Internal Med, Div Rheumatol, Louisville, KY 40292 USA

[5] Univ Florence, Dept Internal Med, Div Rheumatol, Florence, Italy

来源：

RHEUMATOLOGY | 2013年 / 52卷 / 08期

关键词：

systemic sclerosis; pulmonary fibrosis; simvastatin; animal model; reactive oxygen species; COA REDUCTASE INHIBITORS; TO-MESENCHYMAL TRANSITION; ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; CARDIAC FIBROBLASTS; COLLAGEN-SYNTHESIS; TARGETED THERAPY; EPITHELIAL-CELLS; IN-VITRO; STATINS;

D O I：

10.1093/rheumatology/ket144

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Methods. Chronic oxidant stress SSc was induced in BALB/c mice by daily s.c. injections of HOCl for 6 weeks. Mice were randomized in three arms: treatment with HOCl, HOCl plus simvastatin or vehicle alone. Statin treatment was initiated 30 min after HOCl s.c. injection and continued daily for 6 weeks. Skin and lung fibrosis were evaluated by histological methods. Immunohistochemical staining for alpha-smooth muscle actin in cutaneous and pulmonary tissues was performed to evaluate myofibroblast differentiation. Lung and skin concentrations of VEGF, extracellular signal-related kinase (ERK), rat sarcoma protein (Ras), Ras homologue gene family (Rho) and TGF-beta were analysed by western blot. Results. Injections of HOCl induced cutaneous and lung fibrosis in BALB/c mice. Simvastatin treatment prevented both skin thickness and pulmonary fibrosis. Myofibroblast differentiation was also inhibited by simvastatin in the skin and in the lung. Increased cutaneous and pulmonary expression of VEGF, ERK, Ras and Rho in mice treated with HOCl was significantly lower in mice treated with HOCl plus simvastatin. Conclusion. Simvastatin reduces the development of pulmonary fibrosis, potentially modulating adverse lung remodelling, as shown by the reduced deposition of collagen in alveolar septae. Simvastatin also reduces skin thickness in this model.

引用

页码：1377 / 1386

页数：10

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