The Effect Of STAT1,ICAM-1 And STAT1 Antisense Oligonucleotides On Interstitial Pulmonary Fibrosis Of Rat

Part I The research on the expression of ICAM-1 (STAT1-dependent immune-response genes) in the lungs ofrats with BLM-induced pulmonary fibrosis.Objective To evaluate the 'expression and the role of ICAM-1(STAT1-dependent immune-response genes) in the lungs of rats with BLM-induced pulmonary fibrosis.Methods The distribution and the quantity of ICAM-1 expression in rat lungs were determined by immunohistochemical and image analysis. Results After intratracheal instillation of BLM, the expression of ICAM-1 on alveolar epithelium was increased on the 1st day, reached the peak on the 7th day, and remained at high level on the 28th day. The expression of ICAM-1 on bronchus epithelium, micro vascular epithelium and inflammatory cells was also increased. In the meantime, the increased expression of ICAM-1 in the lungs was correlated with the inflammation degree in lung tissue and the total amount of cell in bronchoalveolar lavage fluid (BALF) .Conclusions ICAM-1 in the lung probably took part in the formation of alveolitis and pulmonary fibrosis in the rats with BLM-induced pulmonary fibrosis.Part II The research on STATl Activation in Alveolar Macrophage of Interstitial Pulmonary Fibrosis in RatsObjective To investigate the role of signal transducer and activator of transcription 1 (STATl) in alveolar macrophage(AM) in bleomycin-induced rat pulmonary fibrosis.Methods Fifty adult female wistar rats were randomly divided into two groups: One group was intratracheally instilled with belomycin (BLM), while another group with 0.9% NaCl solution (NS). The concentration of IFN v in BALF and serum was detected by ELISA. The kinetic change of STATl activation in AM was detected by Western-Blot. The expression of STATl and intercellular adhesion molecule-1 (ICAM-1) in AM and in lung tissue was examined by immunohistochemistry.Results 1. There was no difference in the concentration of IFN y in bronchoalveolar lavage fluid (BALF) and serum between BLM and NS. 2. STATl was nearly activated in AM of NS. After bleomycin treatment, the STATl activation of AM was significantly increased on day 1, reached peakvalues on day 7, and then gradually decreased, remaining significantly above NS values on day 28(p<0.05). 3. There was a few positive staining cells for ICAM-1 and STATl expression in AM of NS. After intratracheal instillation of bleomycin, the number of positive staining cells for ICAM-1 and STATl expression in AM was significantly increased on day 1, reached peak values on day 7, and gradually decreased from then on, and it was also higher than that of NS on day 28(p<0.05). 4. A few positive expression for ICAM-1 andSTATl was found in lung tissue of NS, After bleomycin treatment, the ICAM-1 and STATl expression in lung tissue was significantly increased on day 1, reached peak values on day 7, and then gradually decreased, remaining significantly above NS values on day 28(p<0.05).5. There was a significant correlation between STATl activation in AM and the expression of STATl and ICAM-1 in AM and lung tissue the degree of inflammation in lung tissue and the total amount of cell in BALF.6. The STATl expression and the ICAM-1 expression in AM and in lung tissue were significantly correlated with the degree of inflammation in lung tissue and the total amount of cell in BALF.Conclusions STATl was abnormally activated in AM of bleomycin-induced Interstitial pulmonary fibrosis(IPF). The abnormal STATl activation may playa role in the pathogenesis of acute alveolitis and pulmonary fibrosis. Part III The effect of STAT1 antisense oligonucleotides on lung fibroblast proliferation and secreting hydroxyproline. Objective To investigate the effect of STAT1 antisense oligonucleotides on lung fibroblast proliferation and secreting hydroxyproline. Methods Ten adult female wistar rats were randomly divided into two groups: One group was intratracheally instilled with BLM, while another group with NS. After 7day ,ten rats were kille...