| Idiopathic pulmonary fibrosis(IPF) is a progression, usually fatal form of interstitiallung disease characterized by failure of alveolar re-epithelialization, persistence offibroblast/myofibroblasts, deposition of extracellular matrix ,and distortion of lungarchitecture which ultimately results in respiratory failure. Lung interstitial fibrosis inducedby bleomycin is usual animal model. Recently investigations show that alveolarepithelial cell apoptosis might play important role in this disease, which makes Fas/Fas L,caspase-1 and caspase-3 signal pathway abnormal. Basement membrane degradation can beindicative of tissue injury, matrix metalloproteinases are a family of zinc enzymesresponsible for degradation of basement membranes. Extracellular matrix producing cell(such as lung fibroblast) was activated on continue injurys and differented intomyofibroblast. Increasing collagen synthesis and breaking balance of MMPs/TIMP1leads to decrease activity of proteinases and deposition of extracellular matrix, evenfibrosis. In our study, we have illustrated effect of fufangbiejiafang on apoptosis andactivation of metalloproteinases in vivo,in vitro and molecular level. We divided into three parts in vivo. 1, Consecutive change by single-dosedbleomycin-induced pulmonary fibrosis of rats; 2,The experiments study of interventionof fufangbiejiafang(FFBJF) on gelatinases activities from the serum and thebronchoalveolar lavage fluid and the lung homogenate of these rats with lung intertistialfibrosis; 3,BALF apoptosis on lung fibrosis rats induced by bleomycin. We have three aimin vivo study,1,we observed treatment effect of FFBJF.2, we explored about the vivomechanism of gelatinases on fibrosis rats induced by bleomycin; 3, we explored themechanism of apoptosis on fibrosis rats induced by bleomycin.The results showed, 1,some functional injuries occurred before 28 days of a intratracheal instillation(IT) ofbleomycin-induced lung fibrosis model. Model rats had obviously changes of body weightand hypoxemia and disfunction of PS on days 7 and improved on days 14. Hydroxyprolinelevels increased in bleomycin-treated rats on days 14, and Mallory stain was positive .Itmeans lung intertistial fibrosis was caused in 14days. Neutrophils mainly played animportant role in the acute stage of lung injury and marcrophages lympha cells in the chronic stage of pulmonary fibrosis. The media group some degreely improved and PS function . It ameliorate firosis because of inhibition of inflammation.2, The level of MMP 9 was augmented in the fibrosis early stage. MMP 9 activity in the serum and BALF and lung tissue homogenate was highest at 3days than that of 1 and 7days ,there is no signifance between BLM group and control group at 14 and 28days. while the level of BALF MMP2 began to increase after 14days,even 28days.Lung tissue homogenate MMP 2 level began to increase in 3days .serum MMP 2 level had not changed from 1 days to 28days. In some extent, FFBJF may alieorate fibrosis,especially medium dosage drug. Impossible mechanism relied on inhibiting inflammation, but it could not inhibit the activities of MMP 2; 3,from 7 days to 28days, bronchoalveolar lavage fluid had not found apoptosis and cell proliferation. We adopted four steps in vitro We used medium dosage herds based on the conclusion in vivo. 1,the study on secretion metalloproteinases activities that are produced by macrophages of lung fibrosis rat induced by bleomycin. 2,the study on fibroblast of lung fibrosis rat induced by bleomycin. 3,the study on alveolar type II apoptosis of lung fibrosis rat induced by bleomycin. 4,the study on dysfuction mechanism of rat alveolar type II (AT-II) injured by bleomycin. Aim had two kind, 1,to study cell source of MMP2 and MMP9 ;2,to investigate fibrosis rat apoptosis mechanism in advance. We had results showed , 1,MMP 9 level of BLM group 1d,3d,7d macrophage were signicantly increased compared in control group determinated by quantitative ELISA (P<0.05) , while MMP 2 and TIMP 1 had not changed among three group. MMP 9 level of fu...
|
PDF Full Text Request