| Background and Objective Idiopathic pulmonary fibrosis(IPF) is a worldwidely refractory disease with high prevalence, poor prognosis and high mortality. However, its etiology is still not clear. This disease is characterized by diffused alveolar inflammation and structure disturbance of alveolars, which finally result in pulmonary interstitial fibrosis. Current studies reveal that, prominent features of IPF are chronic and progressive pulmonary interstitial proliferation, aggregation of extracellular matrix(ECM) as well as persistent damage of lung function, and the disturbance of ECM degradation and aggregation is the key factor contributing to the abnormal construction of respiratory tracts, persistent damage of lung function and interstitial proliferation. Its pathogenesis is opaque. But transforming growth factor-?1(TGF-?1) is now verified to be the key fibrosis factor. Matrix metalloproteinase-7(MMP-7) is the smallest member of matrix metalloproteinases(MMPs) superfamily and also one of the most important factors. Due to its opaque etiology and pathogenesis, effective treatment is still absent currently. Tetrandrine, abstracted from the root of menispermaceous plants, is a alkaloid subordinated to double benzyl quinoline compounds.It has extensive pharmacological actions, especially the suppression on fibrosis of cytokine, which present a prospective future of the treatment to pheumosilicosis, hepatic fibrosis, portal hypertension, pulmonary hypertention, tumor and regulation of immunity function. Recent researches show that this drug has a good anti-fibrosis action. This study aims to study the influence of tetrandrine on TGF-?1 and MMP-7 in serum and explore the mechanism and therapeutic effect of tetrandrine on IPF through observing the improvement of pulmonary functions, imaging manifestations and clinical symptoms and adverse reactions.Methods This study retrospectively analyzed 62 inpatients and outpatients admitted to Respiratory Department of the First Affiliated Hospital of Zhengzhou University between June, 2012 to June, 2013. All these patients, diagnosed by the criteria of IPF and signed a consent form, were randomized divided into 2 groups and the treatments were as follows:(1)control group: basic treatment and methylprednisone(1mg/kg/d, with the maximum of 60 mg and a tapering schedule of 5mg/w until the maintenance therapy of 10mg/d).(2)treatment group: the treatment of control group in combination with oral tetrandrine(40mg/time, three times a day). After 3 months treatment, changes of therapeutic effect, lung HRCT, TLC, DLco, Pa O2, and adverse reactions were compared. This study also measured serum TGF-?1 and MMP-7 with ELISA. SPSS17.0 software was applied to analyze the data.Results 1. Integral change of main clinical manifestation and sign: The integrals of cough, chest tightness, panting and Velcro rale respectively in treatment group after treatment were(3.00±0.65)scores,(0.83±0.44)scores,(1.22±1.13)scores and(1.14±0.28)scores, while in control group,they respectively were(3.08±0.73)scores,(1.11±0.98)scores,(1.98±1.35)scores and(1.50±0.83)scores. The difference between these two groups had statistical significance(P<0.05).2. Indexes of lung function and blood gas analysis: Measurements of TLC, DLco, and Pa O2 in treatment group after treatment respectively were(58.32±10.98)%,(65.33±2.51)% and(85.12±9.20)mm Hg while in control group, they respectively were(57.02±10.94)%,(54.63±1.53)% and(72.51±3.50)mm Hg. The difference between these two groups had statistical significance(P<0.05). 3. Changes of lung HRCT: Integrals of lung HRCT in control group before and after treatment respectively were(15.48±2.69)scores and(15.38±1.34)scores. The difference between them had no statistical significance(P>0.05). However, those in treatment group respectively were(9.49±2.50)scores and(16.17±4.11)scores. The difference between them had statistical significance(P<0.05). 4. Clinical therapeutic effects: Total effective rate in treatment group was 86.67%, while in control group, it was 64.52%. The difference between them had statistical significance(?2=4.034, P<0.05). 5. Changes of serum TGF-?1 and MMP-7: Measurements of serum TGF-?1 and MMP-7 in treatment group respectively were(13.34±1.83)ng/ml and(84.29±13.56)ng/ml, while those in control group respectively were(19.38±1.72)ng/ml and(78.54±18.93)ng/ml. These two indexes were both dramatically decreased. The difference between the two groups after treatment had statistical significance(P<0.05). 6. Adverse effects: We did not find out obvious adverse effects or toxicities related with tetrandrine in the process of treatment.Conclusions 1. Tetrandrine can improve clinical manifestations, signs and life quality of IPF patients without obvious adverse effects. It has a good clinical therapeutic effect and security. 2. Tetrandrine can inhibit the expression of TGF-?1 and MMP-7, thus lessening the lung fibrosis. Maybe the mechanism is that tetrandrine inhibits Ca2+ from going into cells and reduces the activities of calmodulin, thus decreasing the expression of TGF-?1 and MMP-7. |
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