Preventive And Therapuetic Effects Of Triterpene Acids Of Loquat On Pulmonary Fibrosis Of Rats And Its Mechanisms

Pulmonary fibrosis(PF) is a chronic progressive lung disorder, characterized by parenchymal cell injury and fibrosis of the alveolar parenchyma and a low grade mixed inflammatory infiltrate. The pathogenesis of PF is known to involve destruction of epithelium and the underlying basement membrane, typeⅡcell hyperplasia, fibroblastic/myofibroblasic foci, and excessive extracellular matrix deposition. Epidemiological survey indicated that PF had an average of 2 to 4 years since the symptoms to death, and 5-year survival rate was 30%-50%. Specific treatments for PF are not available, and current treatments only control inflammation and delay the progression of fibrosis. Nowadays, therapy drugs including corticosteroids, immunomodulatory agents are used in clinic;however, their efficacy is limited and they have the disadvantage of long-term side effects.the triterpene acids(TAL) extracted from Eriobotrya japonica (Thunb.) Lindl.leaf were the effective components, which had effect of anti-inflammation, anti-oxidative, relieving cough and asthmaand immunoregulation.Rat model of PF was induced by injecting with a single dose of BLM (5mg/kg) by trachea, prednisone as the positive drug. On that base we study the preventive and therapuetic effects of Triterpene Acids of Loquat (TAL) on pulmonary fibrosis and its partly mechanisms. The main contents are divided into two sections as follows:1.Preventive and therapuetic effects of TAL on pulmonary fibrosis in ratsOne hundred and twenty male wistar rats weighing 250±10g were randomly divided into six groups(n=20) as follows:control, BLM, TAL(450,150,50mg/kg) and prednisone(3.5mg/kg) groups. Except the control group, other groups of rats were injected with a single dose of BLM (5mg/kg)by trachea.From the second day, all the therapeutic groups were treated with TAL(450,150,50mg/kg) or prednisone(3.5mg/kg) respectively. The drugs were dissolved in CMC-Na and in the control group CMC-Na was intragastrically (i.g.) injected instead. Compared with the model group, TAL can significantly reduce lung index, the HA,LN,CIV,PⅢNP and Hyp content in lung homogenates decreased. Histopathological examination and morphological analysis of semi-quantitative results also show that TAL TAL could ameliorate lung formation and alleviate fibrogenesis by hematoxylin-eosin(HE) staining and masson staining.These results suggest that TAL has positively preventive and therapuetic effects on pulmonary fibrosis in rats.2.The effect of TAL on expression of TGF-β1/CTGF in lung tissueFurther study showed that TAL could markedly reduce MDA in serum and increase SOD activity. RT-PCR results also showed that TGDB significantly decreased the mRNA expression of TGF-β1,CTGF in lung tissue, compared with the model group. These results suggested that TAL has positively therapeutic effects, which might be accociated with inhibiting the TGF-β1 and CTGF mRNA expression of lung tissue and reducing the collagen synthesis in pulmonary fibrosis rats.