Abstract
We hypothesised that endothelin (ET)-1 plays an important role in the pathogenesis of emphysema. We attempted to apply ET-1 receptor antagonists to demonstrate and further elucidate the molecular pathogenesis pathways through which ET-1 may cause emphysematous changes.
Sprague-Dawley rats were divided into four groups: control, cigarette smoke extract (CSE), CSE+BQ-123 (a selective endothelin receptor type A (ETA) antagonist) and CSE+bosentan (a mixed ETA/ETB receptor antagonist). The CSE was injected intraperitoneally once a week for 3 weeks, and BQ-123 or bosentan was administered daily for the same duration. The expression of ETA receptor, apoptosis index, caspase-3 activity, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and tumour necrosis factor (TNF)-α and interleukin (IL)-1β concentrations were measured in the lung tissue. The ET-1 levels and antioxidant activity were measured in the serum.
Both BQ-123 and bosentan prevented the development of CSE-induced emphysema, blocked the expression of ETA receptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-α and IL-1β, and improved the biological antioxidant activity in the serum.
Emphysema development is suppressed by ET-1 receptor antagonists. ET-1 may cause emphysematous changes through molecular pathogenesis pathways involving apoptosis, proteinase and antiproteinase imbalance, inflammation and oxidative stress.
- Apoptosis
- emphysema
- endothelin-1 receptor
- inflammatory cytokine
- matrix metalloproteinase
- oxidative stress
Footnotes
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