| Pulmonary fibrosis is a kind of chronic progressive interstitial lung disease with progressive dyspnea, dry cough, shortness of breath and wheezing suppress as the clinical features. The disease can be developed from a variety of lung diseases, a variety of systemic diseases, and the primary disease, idiopathic pulmonary fibrosis. Its main pathological feature is proliferation of fibroblasts and myoflbroblasts, excessive deposition of extracellular matrix. With the popularity of high resolution CT, decoction rate of pulmonary interstitial fibrosis is increasing year by year. Its incidence increases with age. Patients’ survival after diagnosis is commonly 3 to 8 years, and the median survival period is just 3 years. Prognosis of the disease is poor. Except a lung transplant, which is very expensive, there is no other effective treatments, so PF is thought to be a kind of refractory disease by the World Health Organization (WHO). In recent decades, with its mature system of treatment based on syndrome differentiation, Traditional Chinese Medicine plays an important role in the treatment of pulmonary fibrosis. TCM doctors have accumulated rich clinical experience, but we need further accumulation of evidence-based medicine and experimental research data to support. Therefore, exploring the effectiveness of TCM treatment on this disease has very important significances.ObjectiveObserve TCM syndrome characteristics of pulmonary fibrosis (PF) disease to deepen the understanding of PF in TCM clinic with certain evidence-based medicine basis; observe the mechanisms of mentor’s experience priscription Fei Bi Decoction on PF by animoal and cytological experiments.Method1 Clinical syndrome characteristics of PFBased on the international diagnosis standard of idiopathic pulmonary fibrosis and secondary pulmonary interstitial fibrosis, designed clinic research form and collected 116 cases of pulmonary fibrosis patients’ datum in the East Hospital outpatient’s department between 2006 and 2015. Then analyzed symptoms datum by clustering analysis method, and summarized the characteristics of syndrome differentiation of pulmonary fibrosis to provide evidence-based medicine statistics.2 Researches about mechanisms of Fei Bi Decoction’s intervention on PF2.1 Fei Bi Decoction was fed to the Bleomycin-associated lung fibrosis mice to observe and analyze the TCM’s function on lung fibrosis by comparing them with control group, group with no treatment and group with glucocorticoid. The main objectives were normal situation of mice, the death of mice, white blood cell count in bronchoalveolar lavage fluid and the total content of collagen in the mouse lung. Then discussed the possible effects and mechanisms of Fei Bi Decoction on PF.2.2 Using drugs of YKL 40 and INF-γ stimulated lung fibroblasts (MRC5) which were seeded on the decellularized mouse lung scaffold. By observing the growth of MRC5 and expression of proteins, discussed YKL-40’s function in the lung fibrosis process.2.3 Kinds of concentrations of Chinese Medicine including Astragaloside, Tanshinone type Ⅱ A powder, Huangqi injection,Tanshinone type Ⅱ A injection, mentor’s Fei Bi Decoction stimulated MRC5 to observe TCM’s effect on lung fibroblasts.Results1 Clinical syndrome characteristics of PF1.1 SymptomsBased on the patients’datum, there are 60 common symptoms in PF. The most 25 common symptoms with a frequency more than 25% in the order are:cough, shortness of breath, wheezing, phlegm, fatigue, dry mouth, sweating, dry throat, weak cough, chills, insomnia, flustered, easy to be cold, sticky phlegm, aversion to wind, difficult to cough up phlegm, constipation, tinnitus and deafness, purple nails and lips, dizziness, lumbar debility and night sweats.1.2 Syndrome elementsIn TCM syndrome elements, the analyze indicated that the "phlegm", "qi deficiency" "heat", "Yin" and "blood stasis" are the main syndrome factors in patients with pulmonary fibrosis.1.3 Differentiation SyndromesAnalyze indicated there are five clusters of symptoms, and the five clusters could be thought as five differentiation syndromes in TCM.Lung Qi Deficiency and Blood Stasis. The symptoms were cough, phlegm, white sputum, easy to feel weak, pale and dark tongue.Lung Heat and Phlegm. The symptoms were sticky sputum, difficult to cough up phlegm, constipation and slippery pulse.Both Lung Qi and Yin Deficiency. The symptoms were breathing, short of breath, chills, sweats, flustered, easy to be cold, insomnia, aversion to wind, dry mouth and dry throat.Kidney Yin Deficiency. The symptoms were night sweats, dizziness, tinnitus and deafness, lumbar debility and deep or fine pulse.Blood stasis. The symptoms were dark purple lips and nails, dark red tongue.2 Experiments of the functions and mechanisms of Fei Bi Decoction on PF2.1 Fei Bi Dectection could relief the process of BLM-associated lung fibrosis mouse model. It could reduce the number of WBC in BAL of mouse and the content of collagen in the mouse lung.2.2 Hot spot cytokine YKL-40 could promote the growth of MRC5 and help the protein expression of ki67, collagen Ⅰ, α-smooth muscle which usually means fibroblast transferred to be myofibroblast. YKL-40 may play an important role to promote the lung fibrosis process.2.3 Fei Bi Decoction and its main ingredients’s function on the growth of MRC5Astragaloside could inhibit the growth of MRC5. Its inhibition effect was enhanced with the increase of its concentration. When its concentration was 0.078ug/ml, it started to show the inhibition with the rate of 3.06±6.52%. And when its concentration was 200ug/ml, its inhibition rate on MRCS was 12.55±15.22%.Tanshinone ⅡA powder could inhibit the growth of MRC5. Its inhibition effect was enhanced with the increase of its concentration. When its concentration was 10ug/ml, it started to show the inhibition with the rate of 2.17±5.39%. And when its concentration was 160ug/ml, its inhibition rate on MRCS was 72.62±12.29%.Huangqi Injection could inhibit the growth of MRC5. Its inhibition effect was enhanced with the increase of its concentration. When its concentration was 6.25×103ug/ml, it started to show the inhibition with the rate of 8.89±5.88%. And when its concentration was 105ug/ml, its inhibition rate on MRCS was 20.58±9.5%.Tanshinone ⅡA Injection could inhibit the growth of MRC5. Its inhibition effect was enhanced with the increase of its concentration. When its concentration was 0.625ug/ml, it started to show the inhibition with the rate of 11.32±10.35%. And when its concentration was 320ug/ml, its inhibition rate on MRCS was 45.06±37.72%.Fei Bi Decoction could inhibit the growth of MRC5. Its inhibition effect was enhanced with the increase of its concentration. When its concentration was 0.156ul/ml, it started to show the inhibition with the rate of 2.89±14.7%. And when its concentration was 2.5ul/ml, its inhibition rate on MRCS was 66.2±34.75%.ConclusionBased on the 116 cases of pulmonary fibrosis patients’ clinic datum and analyze, it was suggested that the common syndromes of pulmonary fibrosis disease minght include Qi Deficiency and Blood Stasis, Phlegm and Lung Heat, Qi and Yin Deficiency of Lung, Kidney Yin Deficiency, Phlegm and Plood Ptasis Blocking Lung. The TCM syndrome characteristics of Qi Deficiency with Blood Stasis was the most common. Qi Deficiency was the main cause of PF and Blood Stasis was the excess factor becaused of PF’s long developed proceed.Fei Bi Decoction could relief the lung situation of PF mice induced by Bleomycin. The mechanisms might be depression of inflammation and inhibiting the collagen synthesis.Cytosine YKL-40 could promote the proliferation and collagen synthesis of MRC5, and advance the transformation of fibroblasts to myofibroblsts. So it was a promoting cytosine of lung fibrosis. While Fei Bi Decoction and its ingredients could inhibit proliferation of MRC5. Especially, Fei Bi Decoction worked with satisfied and stable effects. Tanshinone also worked with good effects, much better than Huang Qi and Astragaloside.Fei Bi Decoction, which was based on the common syndrome Qi Deficience and Blood Statsis of PF, could relief the fibrosis proceed of lung. Its funchion might be inhibition of the growth of MRC5, depression of inflammation and protein synthesis.
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