Inhibition of porcine pancreatic elastase-induced emphysema by eglin-c.
Eglin-c, a compound that inhibits rat elastase but has little effect on porcine pancreatic elastase (PPE), was employed to examine the role of endogenous elastase in PPE-induced emphysema. Twenty-four female Long-Evans rats were divided into three groups: control (n = 8), PPE (n = 9), and PPE + eglin-c (n = 7). Eglin-c (9 mg/rat) was intratracheally instilled 3 days after PPE treatment, twice weekly, until 3 days before pulmonary function testing. Function tests and lung fixation for morphometric analysis were carried out 15-34 days after PPE treatment. Intratracheal instillation of PPE (400 IU/kg) produced significant increases in functional residual capacity, dynamic and quasi-static compliances, total lung capacity (TLC), and mean linear intercept (MLI), as well as a significant decrease in carbon monoxide diffusion coefficient. However, no significant alterations in quasi-static compliance, TLC, or MLI were found in animals treated with PPE and eglin-c. Three additional groups were used to examine the effects of intratracheal instillation of saline or eglin-c: control (n = 9), saline (n = 8), and eglin-c (n = 10). No significant change in any respiratory parameter was found in either the saline or the eglin-c group, indicating no detectable alteration in pulmonary function caused by either the intratracheal procedure or eglin-c. These data suggest that endogenous elastase is an important contributing factor in the development of PPE-induced emphysema in the rat.
Lai
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YL
Pharmacology and Experimental Therapeutics Division, University of Kentucky, Lexington.
Diamond
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011506:Proteins; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D015843:Serpins; D013552:Swine
D011506:Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C028656:eglin proteinase inhibitors; D010196:Pancreatic Elastase