الفهرس 
Introduction and RationaleOnly 14 pages are availabe for public view
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Abstract
Idiopathic pulmonary fibrosis is a chronic, debilitating interstitial lung disease with unknown etiology. The incidence and prevalence of the disease appear to be increasing. We used BLM-induced lung fibrosis model, which is the best-characterized animal model due to its ability to reproduce many pathophysiological aspects of IPF, good reproducibility and easy induction.
Autophagy is a crucial cellular homeostatic lysosome-dependent process. Autophagy dysfunction and repression leads to proliferation of fibroblasts, transition of myofibroblast from fibroblast, cellular senescence and decreasing degradation of collagen, which are all important in the progression of pulmonary fibrosis. Among several signal transduction pathway for autophagy regulation, mTOR which is a highly conserved kinase.
IRB is a potent selective angiotensin-II type 1 receptor antagonists that shows high affinity and serves as an anti-hypertensive drug. Previous studies reported the antifibrotic effect of IRB in IPF and also its autophagic roles in liver fibrosis. RAPA is a potent inhibitor of mTOR, which has been used to prevent graft rejection in solid organ transplantation due to its immunosuppressive properties. RAPA is also attractive in clinical practice due to its potent anti-fibrotic property.
The therapeutic potential of IRB in the regulation of lung inflammatory/autophagy fibrotic-molecular pathways in IPF was not well-known. Additionally, there was no available data addressing whether induction of autophagy is required for the anti-fibrotic effect of IRB or RAPA in lung fibrosis. So, in the present study, the anti-fibrotic and autophagic effects of IRB versus RAPA regarding the histopathological grading of lung fibrosis, lung TGF-β1levels, hydroxyproline content, p-mTOR, ULK1, LC3-I and LC3-II contents were examined in the BLM-induced rat pulmonary fibrosis model.
In this study, a total of 90 adult male albino Wistar rats were used and subdivided randomly into 9 groups of 10 animals each. Four groups without pulmonary fibrosis included control untreated group of rats were not received any medications and other three groups as treatment control groups received only 0.25 ml PBS by intra-tracheal instillation as a single dose on day (0).