The Mechanisms And Effects Of Interferon Gamma In Rat Model Of Pulmoanry Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a comparatively common representative disease of interstitial lung disease with unknown cause. Its characters are dIPFuse alveolitis and alveolar structure disorder, and those pathological changes could ultimately lead to pulmonary interstitial fibrosis. IPF clinical situation includes progressive dyspnea, dry cough and restrictive ventilatory disorder. IPF is an inexorable process with a mean survival time ranging from 3 to 5 years after the time of diagnosis. At present, the main treatment to IPF are using glucocorticoid and cytotoxicity drug, such as meticorten, azathioprine and cyclophosphamide. But the effect is not definition, only a few patienes show better response to those drugs, and those drugs present fairly dangerous side effect. Because of lacking confirmed or specific therapy, the above-mentioned drugs still occupy chief status.Cytokine network play important role in IPF's occurrenc and development. Some cytokines even play decisive role in regulation and maintenance of pulmonary fibrosis. The ratio of Thl and Th2 cytokine of IPF patient presents severe disequilibrium. Analyses of subset populations of T helper cells within the interstitium of patients with IPF reveal a predominant Th2-type pattern of cytokine production. Thl-type cytokines (such as IFN- y ) are absolutely or relatively fewer when compared with Th-2 cytokines (such as IL-4), suggesting that alterations in T cell subpopulations of Thl and Th2 cells and their associated pattern of cytokine production may contribute to progression of IPF. IFN- y belongs to Thl-type cytokines, and can anti-proliferation, immunosuppress and antifibrosis. Thus, it seems reasonable to target therapy to correct the Th imbalance by offering ectogenesis IFN- y.In order to find out the effects of interferon gamma (IFN- y) on the development of pulmonary fibrosis and its mechanism, we conduct researches in the following five aspects: 1. Reproducing rat model of pulmonary fibrosis, and intervening by offer IFN- y or dexamethasone (DXM); 2. Pathology and transmission electron microscope of rat lung; 3.Immunohistochemistry of transforming growth factor (TGF- ) and fibronectin (FN); 4. ELISA of serum IL-4; 5. Western blot of serum surfictant perotein A (SP-A). Main results and conclusions:1. By injecting bleomycin (BLM) into trachea of rats, we successfully established an pulmonary fibrosis animal model.2. The extent of alveolitis and fibrosis of pulmonary fibrosis rats were quantified by grades. Result showed that alveolitis and fibrosis of pulmonary fibrosis rats becomes more serious with time prolongation. The pulmonary alveolitis and fibrosis of IFN- Y group and DXM group were significantly lighter than BLM group.3. The type II peumonocyte microvillus of BLM group were destroied or disappeared, its lamellar bodies were hyperplasiaed and vacuolized and its basement membrane were twisted and defected. There were only few lamellar bodies vacuolized in IFN- y group and DXM group, and most of their basement membrane were integrity.4. The PO of BLM group was significant decreased, and became more serious with time went by, while the PO of IFN- Y group and DXM group were just slightly decreased.5. Strong TGF- protein expression was detected in bronchiolar epitheliums of BLM group. Large amount of TGF- strong positive alveolar macrophages and interstitial cell (such as fibroblast and myofibroblast) was dIPFerently found at earlier period and later period, this indicates TGF- takes part in acute alveolitis and tissue repair, and plays important role in extracellular matrix overdose deposition. The amount of positive cell of IFN- Y group' and DXM group was significant less than BLM group.6. FN protein was found in epithelial cells, endothelial cell and interstitial cell of BLM group at earlier period, and it was significantly reduced at later period. This indicates increasing FN could accelerate collagen synthesis, and increasing FN deposition is a prelude to more collagen deposition, and FN mainly takes part i...