| The mechanisms of pulmonary fibrosis, a consequence of complex and severe lung injury, are still uncertain. The irreversible end-stage organ failure is a major cause of morbidity and mortality, and treating the progressive fatal diseases is a major challenge in modern medicine. The destruction of alveolar epithelium barrier, inflammatory cell infiltration and disequilibrium on the cytokine-network, and subsequent collagen accumulation may be the common pathway in different types of pulmonary fibrosis. Among numerous cytokines contributing to promote pulmonary fibrosis, transforming growth factorpi (TGF-P1) that is expressed by many inflammatory cells and intrinsic cells, is a fibroblast chemoattractant and is able to exert an effect on fibroblast proliferation. Moreover, it is also the most potent stimulator of fibroblast collagen production. Ginkgo biloba, a traditional Chinese medicine, has many pharmacological activities such as anti-inflammation, anti-allergy and lowering blood viscosity. It has been reported that GbE has protective effect against many fibrotic diseases, which are thought to be related to the reduction of TGF protein expression. Since TGF- was extensivelyexpressed in lung tissue during fibrosis development, it is still unknown about the detailed mechanisms of the effect of GbE on the reduction of TGF-pl in different cell type and in various stage of pulmonary fibrosis.Noticeably, foam cells, which swallow mass of lipid peroxides, are present coincidently with collagen during the development of pulmonary fibrosis. Foam cell , present in atherosclerosis and other chronic fibrotic disease, has many different characteristics from macrophage during the pathologic process , which pushes forward the chronic inflammation process. However, the relationship between the foam cell and fibrosis is still uncertain. Additionally, in vitro foam cells expressing more membrane uPA (urokinase-type plasminogen activator), can release more TGF-(31 than macrophages in presence of plasminogen. One griedient of GbE, flavonoid, is functioned as an effective scanvager of reactive oxygen species and lipid peroxides. Another componet of GbE, ginkgolide is able to suppress platelet aggregation and activation. Moreover ginkgolide is also an specific antagonist to PAF(platelet activating factor) receptor. Lipid peroxidation , as well as platelet aggregation and activation are both the stimulating factors to the foam cell formation. Therefore, we try to apply GbE to bleomycin-induced rats to intervene the formation of foam cells in lung. We investigate wether GbE can down-regulate the expression of TGF-J31 in BALF by decreasing the foam cells number, thereby providingexperimental evidence for clarifying the cell mechanisms of up-regulation of TGF-01 induced by oxidative stress. 1 The investigation on effect of GbE on reduction of TGF-pl expression and against pulmonary fibrosis in rats.Aim To investigate the effect of GbE on the bleomycin-induced pulmonary fibrosis and TGF-01 expression in rats.Methods 32 rats were randomly divided into five groups: control group, BLM 14th group , BLM 30th group , BLM 14th group and GbE 30th group. Firstly, the content of lung hydroxproline was measured and the fibrosis and alveolitis grade was observed to investigate the effect of GbE on the bleomycin-induced lung injury and fibrosis. Using immunocytochemical and immunohistochemical method, we observed the changes of TGF- ]3 1 immunoreactive cell percentage and in BALF and in tissue of rats treating with GbE after intratracheal instillation of BLMA5 on different time point.Results The content of lung hydroxproline (collagen content) in GbE group (15.46?.52 mg.g"1 lung weight) was significantly less than that in BLM group (18.87?.62 mg.g"1 lung weight, P<0.01) on 30th days. In Masson staining, lungs from the control group showed normal construction and few collagenosis. Lungs from BLM group on 30th day showed remarkable tile-like collagen accumulation. While lungs from GbE group showed fewer fibrotic area. Changes of pulmo... |
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