Angiotensin-(1-7)-mediated Mas1 receptor/NF-kappa B-p65 signaling is involved in a cigarette smoke-induced chronic obstructive pulmonary disease mouse model

作者：Zhang, Yong; Li, Yang; Shi, Ce; Fu, Xiaomin; Zhao, Lingdi; Song, Yongping^*

来源：Environmental Toxicology, 2018, 33(1): 5-15.

DOI：10.1002/tox.22454

• angiotensin-(1-7)
• chronic obstructive pulmonary disease
• inflammation
• Mas receptor
• NF-kappa B

Angiotensin-(1-7) [Ang-(1-7)] has been shown to play a significant role in the pathogenesis of lung inflammation via Mas receptor; however, its effect in chronic obstructive pulmonary disease (COPD) remains unknown. To explore the effect of Ang-(1-7) on a cigarette smoke (CS) exposure-induced COPD model, 40 C57BL/6J mice were divided into four groups (n=10) and exposed to air or CS for 8 weeks. After that, they were treated with saline or Ang-(1-7) at 0.3 mg/kg for 2 weeks by subcutaneous infusion using osmotic pump. The day following drug/vehicle challenge, lung function was examined and bronchoalveolar lavage (BAL) was performed. Chemokine (C-X-C motif) ligand 1, interleukin-6, and tumor necrosis factor- protein levels in BAL fluid were determined using ELISA; the corresponding mRNA levels in lung tissues were measured using RT-PCR. Mas1 receptor, pIB, IB, nuclear NF-B-p65 protein, pERK1/2, ERK2, pp38, and p38 proteins expression in lung tissues were examined by immunohistochemical staining and western blotting. Ang-(1-7) challenge had no effect on the decreased lung function and emphysema induced by CS exposure. However, Ang-(1-7) treatment blocked CS exposure-induced lung inflammatory responses and lung fibrosis, as determined by Masson's Trichrome staining. Exposure to CS for 8 weeks caused irreversible loss of lung function and emphysema, which could not be reversed by Ang-(1-7) treatment. Thus, the beneficial effect of Ang-(1-7) may be confined to pulmonary inflammation and fibrosis.

• 出版日期2018-1
• 单位郑州大学