[Effect of amiloride on the pathology of a rat model of chronic obstructive pulmonary disease].
OBJECTIVE
To study the effects of amiloride, an inhibitor of urokinase, on pathological and pathophysiological changes of chronic obstructive pulmonary disease (COPD) model, and to investigate the role of urokinase plasminogen activator system components in the pathogenesis of COPD.


METHODS
Healthy Wistar rats (n = 24) were randomly divided into a control group, a model group and an amiloride group. After 7 weeks, lung function measurements were performed. The total and different white blood cell counts of bronchoalveolar lavage fluid (BALF) were determined, and collagen deposition of lung sections was observed by picrosirius staining. The expressions of u-PA, u-PAR and PAI-1 in bronchial lung tissues were examined by immunohistochemical analysis.


RESULTS
In the model group the expiratory resistance (Re) was significantly higher than that of the control group and the amiloride group, while forced expiratory volume in the 0.3 s/forced expiratory capacity (FEV(0.3)/FVC%) and peak expiratory flow (PEF) were significantly lower than those of the other two groups. Significant increase in total white blood cells and percentage of neutrophils and macrophages in BALF was found in the model group as compared to the control group and the amiloride group. The collagen deposition, mainly type I collagen, in airway walls was significantly increased in the model group. The levels of u-PA, u-PAR and PAI-1 in the model group [(0.166 +/- 0.010), (0.158 +/- 0.024), (0.171 +/- 0.012), respectively] were significantly higher than those in the control group [(0.137 +/- 0.015), (0.122 +/- 0.009), (0.144 +/- 0.005), respectively] and the amiloride group [(0.126 +/- 0.004), (0.120 +/- 0.010), (0.122 +/- 0.004), respectively]. F values were 32.463, 4.094, 79.562 respectively, and all P < 0.001. Moreover, u-PAR protein level was positively correlated with neutrophils in BALF in the model group (r = 0.754, P = 0.031).


CONCLUSIONS
Administration of u-PA inhibitor-amiloride significantly alleviated airway inflammation and the pathological changes in COPD rats, suggesting that the u-PA system components are key mediators regulating the inflammatory reaction and tissue remodeling in the pathological process of COPD.
Han
Xiu-di
XD
Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan 250012, China.
Xiao
Wei
W
Liu
Chun-xi
CX
Xu
Xia
X
Wang
Hong-chao
HC
Xing
Ying
Y
D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D000584:Amiloride; D014568:Urokinase-Type Plasminogen Activator