Mechanism For Triterpene Acids Of Lpquat. Leaf On Therapy Of Pulmonary Fibrosis Of Rats

Idiopathic pulmonary fibrosis (IPF) is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix (ECM), distortion of lung architecture and compromised pulmonary function, leading to respiratory failure. The pathogenesis of this disorder remains incompletely understood. Standard treatment of this disease with corticosteroids and/or cytotoxic agents is generally unsatisfactory. In view of the disappointing drugs and therapeutic options available in IPF, there is an urgent need for new insights into their pathobiology that can be translated into therapeutic alternatives. Through the various signaling pathways that mediate pulmonary inflammation and fibrosis have not been completely elucidated, emerging evidence suggests that pulmonary fibrosis is likely to result from deregulated inflammation and matrix metabolism.The leaf of Eriobotrya japonica (thunb.) lindl, as a traditional medicinal use in the world, has preventive and therapeutic a variety of inflammatory conditions, especially chronic bronchitic(CB) and IPF therapy. The effective components were the triterpene acids(TAL), which from Eriobotrya japonica (Thunb.) Lindl.leaf. TAL had effects of anti-inflammation, anti-oxidative and immunoregulation. TAL has been clinically used as an anti-inflammatory drug and been used to treat chronic pulmonary inflammatory disease in China for a long time. Our previous studies proved that Triterpene Acids of Eriobotrya japonica (Thunb.)Lindl. Leaf had therapy effect of chronic bronchitis(CB) rats, which is related to its antioxide effect and inhibition of inflammatory cytokines and mediators secretion, but the effect of TAL on lung fibrosis and its mechanism remain uncertain. Since there are no effective medicine for lung fibrosis treatment, it is important to investigate the anti-inflammatory effect and mechanism of TAL on lung frbrosis so that to empolder it as a novel medicine for therapy. We had taken a methord which injecting with a single dose of BLM (5mg/kg) by trachea, the positive drug was dexamethasone, in order to make rat model of pulmonary fibrosis. TAL has preventive and therapeutic effects on lung fibrosis, which might be related to its reduction on Tumor necrosis factor-a(TNF-a), transforming growth factor-β1(TGF-β1) expression in AM of pulmonary fibrosis rats. On that base we study the mechanism of triterpene acids of loquat.on TGF-β1 induced lung fibrosis and MAPK signaling way.The article is divided into three sections as follows:1.Effect of triterpene acids of eriobotrya japonica (Thunb.) lindl. leaf on TNF-a and TGF-β1 expression in alveolar macrophage of pulmonary fibrosis ratsAim:The goal of this study was to investigate the therapeutic effect and some mechanism of triterpene acids of loquaton Bleomycin A5-induced pulmonary fibrosis rats. Method:The model of pulmonary fibrosis was induced by injecting with a single dose of Bleomycin-A5 (5 mg/kg) by trachea. Since the second day, rats in therapeutic groups had been treated with the related dose of TAL or dexamethasone. On the 28th day after medication, the rats were killed and HE or masson staining was used to evaluate the degree of pulmonary fibrosis. TNF-a and TGF-β1 level in AM culture supernatant was detected by ELISA. The mRNA expression of TNF-a and TGF-β1 in AM was observed by RT-PCR. Conclusion:TAL could ameliorate lung formation and alleviate fibrogenesis. At the same time, TAL(150,450 mg/kg dose group)could reduce the expression of TNF-a and TGF-β1 obviously in AM of pulmonary fibrosis rats either protein or mRNA level. Effects of TAL on lung fibrosis, which might be concerned with its reduction on TNF-a,TGF-β1 expression in AM of pulmonary fibrosis rats.2.The mechanism of triterpene acids of loquat.on transforming growth factor-β1(TGF-β1) induced lung fibroblast-myofibroblast transdifferentiation and MAPK signaling wayAim:To investigate the effects of triterpene acids of loquat(TAL) on transforming growth factor-β1(TGF-β1) induced human fetal lung fibroblasts transdifferentiation, connective tissue growth factor(CTGF), collagen expression and MAPKs pathway. Method:Cultured human fetal lung fibroblasts (HFL-I) in vitro, assay TAL on HFL-I cell proliferation rate by MTT colorimetric, evaluate the levels of CTGF, a-SMA, col-1, col-3 mRNA in each group by RT-PCR, detect the expression levels of p-ERK/ERK,p-JNK/JNK and p-P38/P38 in each group by western-blotting. Furthermore, through combine TAL and of ERK(PD98059) used as the special inhibitors on human fetal lung fibroblasts (HFL-I) induced by TGF-β1, in order to observe the expression of CTGF and discuss the effect of TAL. Conclusion:TAL can inhibit the activation of HFL-I stimulated by TGF-β1; inhibited the over-expression of CTGF and CⅠ. CⅢ, to reduce the accumulation of extracellular matrix; as well as inhibit and delay the expression of p-ERK, p-JNK and p-P38. TAL could reduce the expression of CTGF induced by TGF-β1 It concluded TAL could reduce the expression of CTGF might be related to the inhibition of ERK signal transduction pathway.