Eglin-c prevents monocrotaline-induced ventilatory dysfunction.

Abstract

The present study was carried out to investigate the relationship between elastase and monocrotaline (MCT)-induced ventilatory dysfunction in rats. To accomplish this, we used an elastase inhibitor eglin-c to suppress the activity of endogenous elastase. Thirty-five young Sprague-Dawley rats were randomly divided into six groups: control, MCT, eglin-c(1), eglin-c(2), eglin-c(1) + MCT, and eglin-c(2) + MCT. Rats in the control group received no treatment. Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 wk before the functional test. Each eglin-c(1) rat was intratracheally instilled with eglin-c (9 mg/rat) twice in 1 wk. Each eglin-c(2) rat was intratracheally instilled with eglin-c (9 mg/rat) five times in 1 wk. Both eglin-c + MCT groups were treated with the combination of eglin-c(1) or eglin-c(2) and MCT. In the MCT group, there were significant decreases in dynamic respiratory compliance, maximal expiratory flow rate at 50% total lung capacity, and the slopes of the maximal expiratory flow-%total lung capacity curve and the maximal expiratory flow-static recoil pressure curve. However, in the eglin-c(1) + MCT and eglin-c(2) + MCT groups, all of the above-mentioned MCT-induced changes were prevented. All ventilatory values of the eglin-c(1) and eglin-c(2) groups were not significantly different from those of the control group. These results demonstrate that eglin-c treatment prevents MCT-induced ventilatory dysfunction and suggest that endogenous elastase may play an important role in MCT-induced inflammation-mediated ventilatory abnormality.