[Perindopril and losartan attenuate bleomycin A5-induced pulmonary fibrosis in rats].
OBJECTIVE
To evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor (AT-1 receptor) blocker on the progression of rat pulmonary fibrosis induced by bleomycin A5.


METHODS
Twenty-four male Wistar rats were randomized into pulmonary fibrosis model, perindopril treatment, losartan treatment and control groups. In the former 3 groups, pulmonary fibrosis was induced via intratracheal injection of bleomycin A5 (5 mg/kg), after which the rats in the perindopril and losartan groups received intragastric administration of the corresponding agents at the daily dose of 2 mg/kg and 10 m/kg, respectively. The rats in the control group had intratracheal injection of normal saline only. In the 4th week, the histological changes of the lung tissues were examined microscopically with Masson staining. Hydroxyproline content in the lungs was measured, and the protein expressions of AT-1 receptor, TGF-beta1 and IkappaBalpha were examined using Western blotting. DNA binding activity of NF-kappaB was analyzed with electrophoretic gel mobility shift assay (EMSA), and zymography was used to assess the activity of matrix metalloproteinase-2 and 9 (MMP-2, 9).


RESULTS
Both perindopril and losartan treatment significantly reduced the pulmonary fibrosis score, content of hydroxyproline, protein expression of TGF-beta1, DNA binding activity of NF-kappaB and MMP-2, 9 activity, and increased cytoplasmic protein expression of IkappaBalpha. Perindopril treatment lowered the protein level of AT-1 receptor.


CONCLUSIONS
Perindopril and losartan may inhibit bleomycin A5-induced pulmonary fibrosis in rats by reducing the protein expression of TGF-beta1 and suppressing the DNA binding activity of NF-kappaB and MMP-2, 9 activity.
Meng
Ying
Y
Department of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Meng
Ying
Y
Li
Xu
X
Cai
Shao-Xi
SX
Tong
Wan-Cheng
WC
Cheng
Yuan-Xiong
YX
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001761:Bleomycin / Q000031:analogs & derivatives; D015153:Blotting, Western; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020913:Perindopril / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; C025703:bleomycetin; D019808:Losartan; D020913:Perindopril