Study On Treating Idiopathic Pulmonary Fibrosis With Fuzhenghuaxian Decoction

Objective: At the guide of "Collateral Disease" theory, to observe the efficacy of treating idiopathic pulmonary fibrosis(IPF) with Fuzhenghuaxian Decoction, and inhibition of pulmonary fibrosis in mice model of bleomycin-induced pulmonary fibrosis, and to explore the mechanism of inhibition of pulmonary fibrosis.Methods: Clinical observation: IPF patients with Qi and Yin Deficiency Syndrome, phlegm lung syndrome, were randomly divided into two groups, the observation group were given Fuzhenghuaxian Decoction treatment and control group acetylcysteine for 3 months,then the clinical efficacy were observed before treatment, a month, two months, three months after treatment, including symptom scores, lung function, six-minute walk test(6MWD), St. George’s respiratory questionnaire(SGRQ) and other changes. Animal experiments: first, established a mouse model of pulmonary fibrosis, then treated with Fuzhenghuaxian Decoction, N- acetylcysteine, and saline. The survival status, weight, shape of the lung, HE staining,and expression of IL-17 A,TGF-β1, IL-17 AmRNA and TGF-β1mRNA were observed in mice lung tissue.Results: Clinical Observation:(l) Quality of Life(SGRQ): Symptoms: the activity,syndrome and impacts scores of observation group improved significantly while no significant improvement in the control group, the quality of life in the observation group were better than the control group(P<0.05).(2) 6MWD of observation group improved significantly while no significant improvement in the control group, the Endurance of activity in the observation group were better than the control group(P<0.05).(3) Assessment of lung function: after treatment, the change of Dlco(%)in the observation group were better than the control group(P<0.05).(4) Efficacy of TCM Syndrome: the clinical efficacy rate of observation group was 83.33%, higher than the 27.78% of control group(P<0.05) by rank sum test. symptom scores: After treatment, symptom scores of observation group improved more than the control group; After treatment, breathing, chest tightness, shortness of breath, cough, sputum, malaise and fatigue, and dry mouth of observation group improved significantly(P<0.05), the control group only cough and sputum.(5) No obvious adverse reactions during treatment groups. Animal experiments:(1) general condition was observed: normal lively, strong and stout, shiny fur good spirits; pulmonary fibrosis mice were showed cough, wheezing(lasting about 3 days), squinting, dull, poor spirit, eating less, curled Arch(lasting about one week).(2) pathological results show: general observation: Two weeks After teatment, the lung tissue of normal group always have pale pink, color uniform, smooth surface, soft texture, and good elasticity, no pathological changes spots, bubbles and other large; while lung tissue of model group and the treatment group were swelling, have more pale color than the control group, big bubble clusters and tip size black red bleeding point on the surface. Four weeks after teatment, lung tissue surface pale, uneven, more visible on the surface of red blood stasis black point tip size, texture hard, elasticity decreased significantly. HE staining: lung tissue of the normal group have complete alveolar wall, transparent bubble chamber which were similar in size, the vessel wall, the bronchial wall and alveolar wall showed no increase in thickness, alveolar and bronchial wall showed a small amount of inflammatory cells, no exudation and fibrosis and other changes;two weeks After treatment, lung tissue of the other group changed,for example, alveolitis, some cell walls rupture, alveolar structure disappeared, alveolar septal thickening, bronchial wall and alveolar septal infiltration of inflammatory cells, and local bleeding;four weeks After treatment, alveolar structure were damaged, alveolar space disappear or pathological fusion expansion, fibroblasts proliferated, cord-like fibrous tissue showed patchy distribution, compared with lung tissue of two weeks After treatment, the inflammation cell infiltration reduced. Both of treatment groups were visible pathological changes similar to the saline group, but had a lesser extent.(3) Comparison of IL-17 A and TGF-β1 expression: The expression of IL-17 A can be observed in mouse lung tissue, locating in the terminal bronchioles and respiratory bronchioles, alveolar epithelium, brownish yellow staining; TGF-β1 expression, positioned at the terminal bronchioles and respiratory bronchioles, alveoli epithelial and pulmonary interstitial, brownish yellow staining. The analysis of positive cells MOD value showed that: Compared with the control group, The expression of IL-17 A, TGF-β1 in other groups increased significantly; Compared with the model group, western medicine group 14 and 28 days IL-17 A, the expression level of TGF-β1 was no difference(P> 0.05); In treatment group at 14 d and 28 d, the expression of IL-17 A and TGF-β1 were lower than the model group and western medicine group(P <0.05).(4) IL-17 A, TGF-β1mRNA compare expression:Compared with control group, in the other groups, expression levels of IL-17 AmRNA and TGF-β1mRNA were significantly increased(P <0.05), pulmonary fibrosis may be prompted with IL- 17 A, TGF-β1 expression in the relevant regulation; Western medicine group compared with the model group, expression levels of IL-17 AmRNA and TGF-β1mRNA were not significantly different(P> 0.05); Compared with the model group, in TCM group expression levels of IL-17 AmRNA and TGF-β1mRNA were decreased(P <0.05)..Conclusion:Fuzhenghuaxian Decoction could effectively improve the clinical symptoms, their quality of life and endurance activities, and reduce the loss of lung function of IPF patients. Animal experiments confirmed Fuzhenghuaxian Decoction may regulate the expression of IL-17 A and play a role in anti-fibrosis.