| Objective: Pulmonary fibrosis is one of serious illness respiratory system. Pulmonary fibrosis is characterized by chronic scar formation and deposition of extracellular matrix(ECM), resulting in impaired lung func- tion and respiratory failure. That is, the characteristics of disease are sedi- ment and contraction of much ECM. Moreover, the process usually need for many years and can cause lung function lost. Currently pathogenesis is unc- lear and the lack of effective treatments. Although the fibrosis is irreversi- ble, pulmonary fibrosis is a chronic and progressive pathological progress. Exploring the pathologic process of the molecular mechanisms of disease in search of new targets to delay or block pulmonary fibrosis progress has important significance.In the development process of fibrosis, transforming growth factor-β(TGF-β) is certain. TGF-βinduces fibroblasts to synthesize and deposit ECM, and for a long time, it is regarded as an important fibrosis response regulator. TGF-β, by regulating the ECM cells transcription, promotes the level of ECM expression, and can induce various cell including fibroblasts to synthesize and secrete ECM and restrain its degradation. However, fibro- sis response signalling pathways via TGF-β, is activated after combining TGF-βand its receptors, then a series of signal transductions are induced and achieve its biological effects. Transforming growth factor-βⅡtype re- ceptor (TGF-βRⅡ) plays a vital role. After combinating with TGF-βin the cell surface, it evoke signalling pathways. Research shows that TGF-βRⅡincludes five isoforms-TβR-Ⅱ, ActR-Ⅱ, ActR-ⅡB, BMPR-Ⅱ, and AMHR-Ⅱ, but which factor involved in the formation of pulmonary fibro- sis, is not yet clear. In this study, bleomycin-induced pulmonary fibrosis in rats as a model to observe expression changes of transforming growth factor-βⅡtype receptor isoforms in the process of pulmonary fibrosis for future clinical treatment of pulmonary fibrosis intervention target.Method: This study could be divided into two steps: 6-week-old and female SD rats, weight 180g-220g, were randomly divided into two groups: instillated with 0.4%BLM 5mg/kg sterile saline intratracheally, respetively six rats sacrificed at 1, 3, 7,14, 28, 35 days after instillation and the lungs harvested; Six rats of normal group at the same time, killed directly. We applicated hematoxylin-eosin (HE) staining to observe pathological changes in lung tissue and used real-time fluorescence quantitative PCR (real-time PCR) analysis of lung tissue TGF-βRⅡexpression of various isoforms.Result: The model of pulmonary fibrosis by BLM was successful and fibrosis was gradually obvious. Real-time PCR analysis of different stages lung tissue TGF-βRⅡexpression of various isoforms. ActR-ⅡA and ActR-ⅡB expression is low in the process of forming fibrosis, and their highest level of expression is less than one time of the normal group. While TβR-Ⅱexpression was hign in the 1st day , reached the peak in the 7th day, then dropped to the low level in the28th day, and increased again, to the 35th day. While AMHR-Ⅱincreased 1 day after underwent BLM, reached peak at 14 days, then dropped. After TβR-Ⅱ, ActR-ⅡA, ActR-ⅡB and AMHR-Ⅱof fibrosis group be compared to the normal group, it had significance (P<0.05). At the same time, comparing each factor of fibrosis group, we found just TβR-Ⅱsignificant (P<0.05).Conclusion: 1. TβR-Ⅱ, ActR-ⅡA, ActR-ⅡB and AMHR-Ⅱare invol- ved bleomycin-induced pulmonary fibrosis in rats. 2. TβR-Ⅱexpression is high in the early period of inflammatory reaction and fibrosis stage, and the hignest expression is seven times of the normal group.
|
PDF Full Text Request