| Background: Paraquat is a bipyridil nonselective contact herbicide with severe toxicity. Paraquat's lethal toxicity has resulted in high mortality rate up to 60% to 87.8%. That is because neither antidotes nor chelating agents which can combine paraquat in blood or tissues have been developed. Acute lung injury is developed because of the lung tissue is damaged by superoxide anions which were generated by paraquat soon after it is ingested. Ingestion of large amounts of paraquat results in rapid death from multiple organ dysfunction syndrome (MODS), but smaller doses often cause a delayed progressive lung fibrosis that is usually fatal and patients die from acute respiratory distress syndrome(ARDS). Although advanced life support measures that applied in modern times decreased the percentages that patients who suffered paraquat poisoning die from MODS, but these methods could neither prevent the development of pulmonary fibrosis induced by paraquat poisoning nor reduce the percentages that patients die from delayed progressive lung fibrosis. The mechanisms of paraquat-induced pulmonary fibrosis and multiple organ failure are not clear at the recent time, but it is thought to be related with the generation of cytokines and oxygen free radical. Therefore, it is urging to study on the mechanisms and effective therapeutics of pulmonary fibrosis induced by paraquat poisoning. Recently, people pay close attention to the effect of the cytokines that generated in the process of pulmonary fibrosis induced by paraquat poisoning and it is reported that multiple cytokines exert their functions in such a pathological procedure. Lung injury and pulmonary fibrosis are inevitable consequences of paraquat poisoning, but there were seldom drugs that have confirmed to have the functions to prevent pulmonary fibrosis or improve lung edema and hemorrhage have been clinically studied up to now.Xuebijing Injection is an intravenous preparation which is refined and screened from 32 prescriptions of traditional Chinese medicine. The components of Xuebijing Injection are Chinese crude drugs of Flos Carthami, Radix Paeoniae Rubra, Rhizoma Chuanxiong, Radix Salviae Miltiorrhiae, Radix Angelicae Sinensis and Herba Houttuyniae and it has the functions to activate blood circulation to dissipate blood stasis and deoppilate meridian. It is wildly used in the treatment of serious diseases such as systemic inflammatory response syndrome (SIRS) and MODS clinically. Its active ingredients include safflor yellow A, ligustrazine, tanshinol, ferulaic acid and peoniflorin. Ferulaic acid exerts the functions to eliminate oxygen free radical (OFR) and prevent pulmonary fibrosis. Ligustrazine has the effects to prevent ischemia reperfusion injury and ARDS as well as ALI by eliminating OFR. Tanshinol can resist anoxic vasoconstriction and prevent ARDS. Xuebijing Injection is highly effective in resisting endotoxin and it has great functions to resist endogenous mediators of inflammation out-of-control releasing from mononuclear macrophage induced by endotoxin. Besides, Xuebijing Injection can inhibit the expression of procollagen mRNA, decrease the content of lipid peroxidation, increase the activity of superoxide dismutase(SOD), reduce the generation of fibroblast, inhibit the sedimentation of extracellular matrix so as to reduce the expression of transforming growth factor-β1 and inhibit the development of pulmonary fibrosis. Similarly, there were seldom studies reported the use of Xuebijing Injection in the treatment of pulmonary fibrosis induced by paraquat poisoning and its mechanism of anti pulmonary fibrosis has not been researched thoroughly.Objective: The purpose of this study is to treat patients who suffered parapuat poisoning with Xuebijing Injection at the early period of the disease and the concentrations of serum transforming growth factor-β1 (TGF-β1) and typeⅢprocollagen peptide (PⅢP) as well as the respiratory function, the accumulative score of lung high resolution computerized tomography (HRCT), the incidence rates of pulmonary fibrosis, the degree of pulmonary fibrosis and the fatality rates of the patients who suffered paraquat-induced pulmonary fibrosis are determined and compared within and between each groups so as to approach the effect of cytokines in the pathogenesis of pulmonary fibrosis induced by paraquat poisoning and to estimate the clinical curative effect of Xuebijing Injection in the treatment of paraquat-induced pulmonary fibrosis through regulating cytokines and the expression of genes.Methods: 36 patients whose diagnoses were acute paraquat poisoning and were hospitalized and treated in the department of emergency of China-Japan Union Hospital during February 2007 to February 2009 were included in the research and were randomly divided into two groups as a conventional therapy group including 19 cases and a Xuebijing group including 17 cases and another 20 health examination cases that were chosen from out-patient department were served as a control group. No statistical differences of the items such as gender, age, the dose of the poison ingested, the time elapsed from morbidity to gastric lavage and the time elapsed from morbidity to medication were found therefore comparability exists between the three groups. Patients in the conventional therapy group were treated conventionally with gastric lavage, catharsis, hemoperfusion, antioxidants and glucocorticosteroid immediately after admission. For the patients in Xuebijing group, besides conventional treatment, Xuebijing Injection was given with a dosage of 50ml added in saline with a dosage of 100ml every 12 hours for 14 days. Blood was taken from ulnar vein of the patients in conventional therapy group and Xuebijing group immediately after admission and at the 5th, 10th and 14th day after poisoning and serum that was obtained by centrifugal separation together with the serum obtained from the cases in the control group through the same procedure was preserved in subambient temperature. The concentrations of serum TGF-β1 and PⅢP were determined by enzyme linked immunosorbent assay (ELISA). At the same time, the vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory volume in one second/forced vital capacity (FEV1/FVC), diffusion capacity for carbon monoxide of the lung (DLCO), arterial partial pressure of oxygen (PaO2) and lung computerized tomography (CT) examination of the patients in conventional therapy group and Xuebijing group were determined at the 5th, 14th and 30th day after poisoning. The indexes mentioned above as well as the respiratory function, the accumulative score of lung HRCT, the incidence rates of pulmonary fibrosis, the degree of pulmonary fibrosis and the fatality rates were compared within and/or between the three groups.Results:①Compared within the conventional therapy group and the Xuebijing group, the concentrations of TGF-β1 and PⅢP in the serum that was obtained from the patients who suffered paraquat poisoning instantly after admission and at the 5th, 10th and 14th day after poisoning had a tendency to increase gradually as the pathological procedure is in process and the differences possess statistical significance (all P<0.01). Compared between the three groups, the concentrations of serum TGF-β1 and PⅢP of the patients in conventional therapy group and Xuebijing group instantly after admission and at the 5th, 10th and 14th day after poisoning were significantly higher than that of the control group (all P<0.01) but the cytokines mentioned above of the patients in Xuebijing group at the 5th, 10th and 14th day after poisoning were obviously lower than that of the conventional therapy group at the corresponding time period and all differences possess statistical significance (all P<0.01).②The values of the respiratory function indexes such as VC, FVC, FEV1, FEV1/FVC, DLCO and PaO2 of the patients in conventional therapy group at the 14th and 30th day after poisoning were significantly lower than that of the 5th day after poisoning (all P<0.01 or P<0.0.5) but there were no statistical differences of the items mentioned above of the patients in conventional therapy group at the 14th day after poisoning when they were compared with the 30th day (all P>0.05). There were no differences of the respiratory function indexes mentioned above at the 14th and 30th day after poisoning comparing with the 5th day within Xuebijing group (all P>0.05) but they were evidently higher than that of the conventional therapy group at the corresponding time period and all differences possess statistical significance (all P<0.05 or P<0.01).③Compared within the conventional therapy group and the Xuebijing group, the accumulative score of lung HRCT at the 14th and 30th day after poisoning were significantly higher than that of the 5th day after poisoning and increased gradually as the the pathological procedure of paraquat poisoning is in process and all differences possess statistical significance(all P<0.05 or P<0.01). Compared between the conventional therapy group and the Xuebijing group, the accumulative score of lung HRCT of the patients in Xuebijing group at the 14th and 30th day after poisoning were evidently lower than that of the patients in conventional therapy group at the corresponding time period and all differences possess statistical significance(all P<0.01).④The incidence rate of pulmonary fibrosis, the degree of pulmonary fibrosis as well as the fatality rate of the patients in Xuebijing group were significantly lower than that of the conventional therapy group and the differences possess statistical significance (all P<0.05 or P<0.01).Conclusion: The concentrations of serum TGF-β1 and PⅢP of the patients who suffered paraquat poisoning are obviously increased at the early period of the disease and trend to increase gradually as the pathological procedure is in process. These results indicate that cytokines such as TGF-β1 and PⅢP play great role in the pathological procedure of paraquat-induced pulmonary fibrosis. But the fact that the concentrations of the cytokines mentioned above declined evidently when Xuebijing Injection is given to such patients illustrates that the development of pulmonary fibrosis induced by paraquat poisoning can be inhibited by Xuebijing Injection through regulating cytokines and the expression of genes. Xuebijing Injection has the functions to improve respiratory function, lessen the pulmonary pathological injury induced by paraquat poisoning, decrease the incidence rates of pulmonary fibrosis, depress the degree of pulmonary fibrosis as well as the fatality rates of paraquat poisoning so as to improve the prognoses of the patients who suffered paraquat poisoning if it is used at the early period of the treatment.
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