| Objective:Radiation therapy (radioactive, therapy, RT) is one of the treatment of chest tumor,such as lung cancer, breast cancer, esophageal cancer.The lung is a radiation sensitive organs in the human body, radiation therapy can make the lung tissue near the tumor take more than the biological effects of radiation dose threshold and cause cell damage in different degree. Radiation-induced lung injury (radio-pulmonary lesion, RPI) is one of the common complications of the chest tumor radiotherapy, patients usually has two kinds of forms, early stage of acute radiation pneumonia and later stage of radiation pulmonary fibrosis. Radiation-induced lung injury limits the dose of radiotherapy of tumor, the radiation effect is greatly reduced, and its pathogenesis is not clear, and the lack of significant predictors.It has become a big problem in the effective treatment of chest tumor. Once the occurrence of radiation-induced lung injury, using adrenal cortical hormone and antibiotic is the most commonly method of clinical treatment. Although a large dose of hormone may temporarily alleviate symptoms, inhibit the development of pulmonary fibrosis, but easily lead to many complications. Radiation-induced lung injury occurs often irreversible, so prevention is more important than treatment. Recent studies show that a variety of cells, cytokines and inflammatory medium interaction occurred in the process and development of radiation-induced lung injury. Because of many links and the complexity of its pathological mechanism, effect of single link or targeting is not ideal, still lack specific clinical drug for prevention of radiation-induced lung injury. Amifostine (AMSF) is now recognized as the world’s only more mature in the clinical application of radioactive lung injury protective agent. Unfortunately, amifostine is expensive, few patients can afford, significant side effects, It can not be widely used clinical. Therefore, searching for radiation-induced lung injury protective agent which need low toxicity and high economy, becomes increasingly important. Chinese medicine is the treasure of traditional Chinese medicine in China.It has the characteristics of overall regulation. Chinese medicine has good effect and prospect in radiation-induced lung injury. Many clinical studies show that, the curative effect of Chinese medicine can effectively improve the clinical symptoms, improve the quality of life, reduce the mortality rate, so research of traditional Chinese medicine for treatment of radiation-induced lung injury has a very important practical significance. Bailing capsule is cultured Cordyceps mycelia, traditional Chinese medicine preparation made by biological engineering method, chemical composition and its effects and natural Cordyceps basic consistent, decades of studies have confirmed, Bailing Capsule has played a certain role on immune regulation, anti-tumor, anti radiation. Research confirms that it can significantly reduce the important cytokine fibrosis transforming growth factor β (TGF-β), have certain effects on the improvement of kidney and liver fibrosis. The mechanism of Bailing Capsule for treatment of radiation-induced lung damage has not yet reported. This paper is divided into two parts, the first part is based on observation of Bailing Capsule treatment of radiation-induced lung injury in rat model.MethodThe first part is basic research:141male SD rats of clean degree, were randomly divided into normal control group (control group), simple radiation model group (model group), Bailing Capsule in the prevention group (bailing prevention group), bailing capsule treatment group (100treatment group), dexamethasone treatment group (dexamethasone treatment group), with21rats in the normal control group, other groups were30. Each group were given X ray chest single irradiation20Gy, normal control group except. Bailing Capsule with physiological saline solution into certain concentration suspension. The normal control group, model group after modeling the very next day to equal volume of saline, bailing treatment group were administrated with Bailing capsule suspension, dexamethasone treatment group was treated with oral dexamethasone suspension,1times a day. Bailing prevention group in irradiation for1weeks before beginning gavage of Bailing Capsule suspension. Each group respectively at2,4,6weeks the rats were sacrificed at different time points randomly,7rats in the normal control group, other groups were10, rats were intraperitoneally injected with10%chloral hydrate anesthesia solution, from the heart of5ml, the heparin anticoagulant tubes,4℃3000r/min centrifugal separation of plasma,10min,-20℃refrigerator for save. Acquisition of lung tissue in rats, weighing, changes of lung coefficient; the pathological changes of lung tissue in rats was observed under light microscope by HE staining, ELISA assay was used to detect the changes of rat plasma TNF-α, IL-6and TGF-β1content. Immunohistochemical staining of lung tissue in MMP-2rats, TIMP-2expression, change detection of lung SOD activity, MDA content and chemical colorimetric method. The second part:To observe the clinical study from2012March to2012August from First Affiliated Hospital of Gannan Medical College oncology patients receiving thoracic tumor radiotherapy, a total of38cases, were randomly divided into two groups:bailing capsule group (19cases)--radiation while taking Corbrin capsule, from the first day to start taking radiotherapy, according to500mg/kg, oral,3times per day, continuous service to one month after the end of radiotherapy. The control group (19cases)--radiotherapy. To observe the incidence of radiation pneumonitis, TGF-p1levels, TCM clinical symptom score, quality of life index evaluation.Result.The first part:(1) Based on10Gy,15Gy,20Gy group rats survived, the rats in25Gy group at2weeks after irradiation have died, in1to4weeks after irradiation has presented the acute inflammatory response,20Gy is the most typical, combined with the general condition of rats were observed, suggesting that20Gy irradiation agent amount the successful production of radioactive lung injury model of rats in a relatively short period of time, provides the basis for screening mechanism and prevention and treatment of drug research in Chinese medicine in prevention and treatment of radiation-induced lung injury.(2) Bailing capsule could significantly reduce the lung coefficient of radiation pneumonia rats (P<0.01), bailing prevention group than bailing treatment group, prevention group, bailing bailing treatment group, dexamethasone treatment group differences have statistical difference (P<0.05). Pulmonary histopathology observation shows that, bailing prevention group, bailing treatment group compared with the model group, inflammatory cell infiltration, alveolar congestion, exudation, hemorrhage and to a lesser extent. Septal hyperemia alveolar treatment group at second weeks of dexamethasone, bleeding relatively model group had no significant difference, but the infiltration of inflammatory cells is relatively light,4and6weeks, the difference was not significant. Second,4,6weeks of relatively bailing treatment group, bailing prevention group, inflammatory degree is heavy. Dexamethasone treatment group fourth week abscess, increased sixth weeks of small abscess, consideration is due to decreased immunity induced by dexamethasone, concurrent infection. The normal control group, clear structure, Bronchial Alveoli and alveolar septum organizational structure is normal, without infiltration of neutrophils in the alveolar septum, no congestion, edema and acute and chronic inflammation change. Each time point were no obvious pathological changes.(3) Compared with the normal control group, SOD activity in lung tissue of rats in model group decreased (P<0.01), the content of MDA increased (P<0.05); compared with the model group, the prevention group,100%in treatment group, dexamethasone treatment of SOD activity was inc reased in lung tissue of rats (P<0.01), the content of MDA reduce (P<0.01). The activity of SOD:bailing prevention group was higher than that of Bailing treatment group, dexamethasone treated group (P<0.01). Bailing treatment group was higher than that of dexamethasone treated group (P<0.05). MDA content:bailing prevention group was lower than that of Bailing treatment group, dexamethasone treated group (P<0.01), bailing in treatment group was lower than the dexamethasone group (P<0.05). (4) Compared with the normal control group, TNF-α, IL-6β and TGF-in plasma of rats in model group were2,14,6weeks were significantly higher (P<0.01). Compared with the model group, the prevention group,100%in treatment group, dexamethasone treatment of TNF-α, IL-6and TGF-β in rat plasma group1was significantly decreased (P<0.01or P<0.05). Bailing prevention group was lower than that of Bailing treatment group, dexamethasone treated group (P<0.01), bailing in treatment group was lower than the dexamethasone group (P<0.01).(5) Compared with the normal control group, MMP-2protein, TIMP-22to4weeks of lung tissue in rats of model group (P<0.01) expression were increased, but MMP-2/TIMP-2ratio increases gradually.4weeks later, MMP-2protein in lung tissue of rats in the model group decreased and TIMP-2expression increased gradually, MMP-2/TIMP-2ratio becomes small. Compared with the model group, the prevention group,100%in treatment group MMP-2, TIMP-2protein expression decreased obviously (P<0.01or P<0.05), MMP-2/TIMP-2balance. Bailing prevention group at2,4weeks than bailing treatment group, no significant difference in sixth weeks. Bailing the treatment group was better than dexamethasone treated group (P<0.01). Compared with MMP-2, TIMP-2with the model group, dexamethasone treatment changes group at each time point, no significant difference (P>0.05). Bailing prevention of MMP-2protein in lung tissue of rats, the expression of24weeks than bailing treatment group (P<0.05at2weeks,4weeks,6weeks of P<0.01) is not obvious (P>0.05). Bailing prevention of TIMP-2protein expression in lung tissue of rats for2weeks and Corbrin group there was no significant difference (P>0.05),4,6weeks a preventive group than in treatment group (P<0.05to4weeks,6weeks P<0.01). Bailing prevention of MMP-2protein expression was lower than the lung tissue of rats with dexamethasone treatment group (2P<0.01,4weeks,6weeks, P<0.05) bailing prevention group rats TIMP-2protein expression in lung and dexamethasone treatment group compared with2weeks no significant difference (P>0.05),4,6weeks a prevention group was lower than that of animal treatment group (P<0.01). Bailing treatment of MMP-2protein expression in lung tissue of rats2weeks than dexamethasone treated group (P<0.05),4,6weeks is not obvious (P>0.05). Bailing treated rats TIMP-2protein expression in lung and dexamethasone treatment group compared with2in4weeks, no significant difference (P>0.05),6weeks a treatment group was lower than that of dexamethasone treated group (P<0.05).(6) Compared with the normal control group, model group, the expression of MMP-2mRNA in lung tissue of rats were increased (P<0.01); compared with the model group, the treatment of pulmonary tissue of rats in each group the expression of MMP-2mRNA was significantly reduced (P<0.01). Bailing prevention group and treatment group was no significant difference of Bailing (P>0.05); bailing the treatment group was better than dexamethasone treated group (2P<0.01,6weeks,4weeks P<0.05).The second part of clinical research:(1) in the radiation pneumonia incidence, chest tumor radiotherapy6weeks after the end of Bailing group, radiation pneumonia incidence was significantly lower than the control group (P<0.05).(2) In TCM clinical symptom score evaluation, bailing group treatment of cough, sputum, bloody sputum, chest tightness, shortness of breath, chest pain and dysphoria heat and other symptoms, at3weeks after treatment and6weeks after a first weeks significantly improved,(P<0.05); bailing group in the third week after radiotherapy and the control group comparison, cough, sputum, bloody sputum, chest tightness shortness of breath, chest pain is the improved significantly (P<0.05); in group sixth week after radiation with control, cough, sputum, bloody sputum, chest tightness shortness of breath is the significant improvement (P<0.01).(3) In the evaluation of life quality, improve, stable in quality of life of Corbrin group were higher than that of control group, reduced quality of life than those in the control group, bailing group was higher than that of the control group, there were significant differences (P<0.05).(4) In comparison to TGF-β1levels in plasma of patients with radiotherapy, bailing group chest radiotherapy in patients with plasma TGF-β1levels were significantly lower than those in the control group,(P<0.01), radiotherapy for6weeks the serum TGF-β1was significantly lower than that of the control group,(P<0.01). Conclusion:The first part:basic research of Bailing Capsule on rats with radiation-induced lung injury has certain effect. The preventive and therapeutic effects may be achieved through the following ways:enhancing the activity of SOD in lung tissue of rats, reduce the content of MDA in plasma; inhibition of proinflammatory cytokines IL-6, TNF-α and profibrotic cytokine release of TGF-β1; reduce the expression of lung tissue in MMP-2rats, TIMP-2protein of radiation-induced lung injury, adjusting the MMP-2/TIMP-2balance. Inflammatory reaction of different extent inhibit or alleviate alveolar, and can inhibit pulmonary fibrosis, the effective ways of protecting the lung tissue so as to reduce the damage, and prevention is better than cure, prevention is better than that of dexamethasone, without any side effect.The second part:clinical study of Bailing capsule has certain effect on radiation-induced lung injury in patients with chest tumor. The preventive and therapeutic effects of mainly the following aspects:bailing group can reduce the incidence of patients with chest tumor radiation pneumonia, down-regulate TGF-β1levels, reduce the clinical symptoms of integral evaluation, improve the quality of life. |
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