| Objective Pulmonary fibrosis is a hardly treated disease which seriously threatens human health with increasing incidence and high death rate. The therapeutic approach to this disease is not particularly effective in western medicine because of its unclear pathogenesis and mechanism. Traditional Chinese medicine has reached a several achievements in improving symptoms and reducing death rate, and it is necessary to summarize and improve the methods of TCM for this disease. Huaxian decoction (HD), a composite recipe of tonifying qi and regulating yang, smoothing qi invigorating blood and eliminating sputum, has shown a bright future in clinical study. In this study, we extensively investigate the effects of HD on the expression of MMP-9,TIMP-1,MMP-2,HYP,PDGF,TGFβ1 in pulmonary fibrosis rats induced by blyomicin to evaluate its curative effect objectively and explore its probable way and mechanism.Methods One hundred and forty-four healthy Wistar rats weighted from 180 to 220 grams were randomly divided into six groups(n=24, each): normal control group, model group, prednisone group, HD groups of high, moderate and low dosage. The rat model was induced by bleomycin and respective medicine was given to each group. Every group was subdivided into three groups (n=8) which was killed in the 7th, 14th and 28th day respectively. The rat's lung tissue section was observed under light microscope and electron microscope to study the alternation of pathological morphology; the pulmonary coefficients were observed respectively; the expressions of MMP-9 and TIMP-1 were detected with immunohistochemical method of analysis; the expressions of PDGF,TGFβ1 were assayed with ELISA method; the contents of HYP were measured with method of specimen alkali hydrolysis; the expressions of MMP-2mRNA were studied with RT-PCR method; and effects on above items of HD were observed.Results (1)HD may significantly reduce the pulmonary coefficients of rats with pulmonary fibrosis induced by bleomycin (P＜0.01). There was significant difference between HD high and low dosage group (P＜0.05). Changes of pathologic morphogenesis under light microscope and electron microscope had shown improvement in prednisone group and HD groups. There were significant differences among groups in Szapiel grade of alveolitis and fibrosis (P＜0.01 or 0.05). The pathologic change of alveolitis from the most obviously to the most slightly was model group, HD low dosage group, HD moderate dosage group, prednisone group, HD high dosage group, normal control group, while that of fibrosis was model group, prednisone group, HD low dosage group, HD moderate dosage group, HD high dosage group, normal control group. (2) In the 7th,14th and 28th day, percentage of positively reaction cell of MMP-9,TIMP-1 was markedly higher in model group than in normal control group (P＜0.01), and it was also markedly higher than in prednisone group and HD groups (P＜0.01 or 0.05), which were significantly higher than normal control group. (3)Contents of PDGF and TGFβ1 in each phases in model group were significantly higher than in normal control group respectively (P＜0.01). Those in prednisone group and HD groups were much lower than in model group (P＜0.01), but those were higher than in normal control group (P＜0.01). (4) Contents of HYP in model group were higher than in normal control group(P＜0.01 )in each phase respectively, and they reached their peak in the 28th day. In prednisone group and HD groups, those were markedly lower than in model group (P＜0.01), though those were higher than in normal control group (P＜0.01). (5) Expression of MMP-2mRNA could be observed in each group in each time. It was obviously higher at the 7th day in model group than in normal control group (P＜0.01), and it reached its peak in the 14th day. In the 28th day, it was still markedly higher than in normal control group (P＜0.01). In prednisone group and HD groups, it was obviously lower than in model group (P＜0.01).Conclusion MMP-9,TIMP-1,MMP-2,HYP,PDGF and TGFβ1 may play important roles in the course of rat pulmonary fibrosis induced by bleomycin. HD can prevent and treat pulmonary fibrosis. This effect could be carried out by following ways: Reduce expression of MMP-9 and TIMP-1 in pulmonary tissue and adjust the system of MMP-9/TIMP-1 to reach its equilibrium; Decrease content of PDGF and TGFβ1; Restrain HYP from over-depositing in the pulmonary tissue; Reduce the expression of MMP-2mRNA in the pulmonary tissue. HD may adjust over-depositing of extra cellular matrix in the pulmonary tissue and protect the normal pulmonary morphogenesis with poly-link and poly-target, so as to play an active role in preventing and treating pulmonary fibrosis. |
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