Clinical Research Of Curcumin Against Paraquat Induced Lung Fibrosis

Objective:In recent years, paraquat poisoning reports are presenting an increasing trend,which owns the feature of "toxic dose small, nor-effective antidote, nor-effective therapy currently, "after poisoning, it mainly prominently damange the lungs of patients.But the exact injury mechanism is currently not clarified.In this study, by monitoring the content of serum matrix metalloproteinase-9 (MMP-9), serum matrix metalloproteinase inhibitor (TIMP-1) and lung imaging (lung HRCT) changes of curcumin intervention paraquat poisoning (PQP) patients, analyse the possible pulmonary fibrosis mechanism and evolutionary process in patients with PQP.Preliminary research into the intervention effects of curcumin on the pulmonary fibrosis in PQP patients to reveal the mechanism of pulmonary fibrosis induced by paraquat, to find an ideal target for treatment and drugs to make a useful attempt.Methods:Collected from March 2008 to March 2010 PQP patients admitted to our department a total of 61 patients (no original pulmonary disease), divided into non-curcumin group (n= 30) and curcumin group (n = 31), non-curcumin group are treated with gastric lavage, blood perfusion, methylprednisolone, vitamin E, C, diuretic, cardiac nutrition, maintaining water and electrolyte, acid-base balance and other conventional treatments. In addition to the conventional treatments above,curcumin group are for curcumin capsules 1000mg, three times a day oral administration, taking 1,3,5,7,14d fasting venous blood 5ml to monitor the content of serum MMP-9 and TIMP-1 levels of the two-group patients with ELASA.Meanwhile, taking the1,3,5,7,14d lung HRCT of the two-group patients,recording matte shadow,grid shadow, honey-combing,and other sighs of lung HRCT,statisticsing on HRCT scores according to Goddard scoring standard.Respectively compare the differences of MMP-9,TIMP-1 and HRCT scores interclass and intraclass of the two groups. Respectively compare the correlation of MMP-9,TIMP-1 and HRCT scores interclass and intraclass.Statisticsing on the 14th day mortality rate of two groups,and the incidence of pulmonary fibrosis of the 5th day after admission.Analysis of the 14th day living conditions of these two groups,curve and depict the survival curve.Results:Compared 1,3,5,7,14 days MMP-9 levels within each group of non-curcumin group and the curcumin group,the differences were statistically significant (P<0.05).Between the two groups except the 14th day, (P>0.05) no significant difference, the rest were statistically significant (P<0.05),MMP-9 of non-curcumin group from the first day began to increase and 3th day peak,curcumin group5th day peak,then gradually reduced. Compared 1,3,5,7,14 days TIMP-1 levels within each group of non-curcumin group and the curcumin group,the differences were statistically significant (P<0.05),showed an increasing trend over time,between two groups all statistically significant(P>0.05),curcumin levels of serum TIMP-1 were significantly lower than that of non-curcumin group.TIMP-1 from the first 1d began to increase, then gradually increasing. Compared 1,3,5,7,14 days HRCT scores within each group of non-curcumin group and the curcumin group.In addition to curcumin group scores between 3 and 5 days, P>0.05, are not significant, all the rest P<0.05 is statistically significant.Between the two groups,in curcumin at different time points the patients HRCT scores were lower than at the same time non-curcumin group patients (P<0.05).Fibrosis was slightly reduced compared with non-curcumin group,the differences were statistically significant. Analysising the correlation of HRCT scores and MMP-9,TIMP-1 at different time within each group of non-curcumin group and the curcumin group.Non-curcumin group of 1,3,5 day after admission lung HRCT scores were positively related to MMP-9 at the same time points,7,14 days were negatively correlated, non-curcumin group of 1,3day after admission lung HRCT scores were negatively related to TIMP-1 at the same time points,5,7,14 days were positively correlated,curcumin group of 1,3,5 day after admission lung HRCT scores were positively related to MMP-9 at the same time points,7,14 days were negatively correlated, curcumin group of 1day after admission lung HRCT scores were negatively related to TIMP-1 at the same time points,3,5,7,14 days were positively correlated.Comparing the incidence and degree of pulmonary fibrosis on 5th day between curcumin group and no-curcumin group, The incidence of pulmonary fibrosis curcumin group (P=0.034<0.05) and fibrosis (P=0.0038<0.01), were significantly lower than non-curcumin group, the difference was statistically significant. Comparing the 14th day mortality and living conditions between curcumin group of patients and non-curcumin, two groups no significant difference in mortality, but survival time of patients curcumin group significantly longer than non-curcumin group.Conclusions:Serum MMP-9 levels of PQP patients increased significantly after the poisoning,3th day peak, then gradually reduced and serum TIMP-1 levels increased after poisoning, with the progression of the disease showed a trend of continuous increase,which indicates that the MMP-9 and TIMP-1 may be involved in paraquat induced lung fibrosis and progress of the startup process.Serum MMP-9 and TIMP-1 levels and pulmonary HRCT score of patients with paraquat poisoning correlated,MMP-9 and TIMP-1 can be used as biochemical markers in clinical combining with CT examination and other means of pulmonary fibrosis and to assess the degree and the prognosis of pulmonary fibrosis early intervention treatment with curcumin on paraquat poisoning patients can reduce the cycle of MMP-9 and TIMP-1 levels,reduce pulmonary fibrosis in patients with poisoning,delay the progression of the disease, prolong survival time,but can not reduce mortality,can not improve prognosis.