| Purpose:To discuss the expression and clinical significance of MMP-9, TIMP-1 among different risk factors in radiation-induced lung injury after lung cancer patients received different doses of radiation therapy.To observe the expression of MMP-9, TIMP-1 in radiation-induced radiation injured mice after received at high altitude district, and to explore the its difference of MMP-9, TIMP-1 in different doses of radiation; To observe the prevention effect in radiation-induced lung injured mice after the intervention of glutathione, and possible related injuries mechanism of RILI.Methods:General information of patients with non-small cell lung cancer receiving radiation therapy was collected in Tumor Hospital of Qinghai University Radiotherapy department from May 2014 to February 2015 and 54 patients were recruited. Univariate chi-square and multivariate Logistic analysis were applied in patients developed RILI. Related analysis information including age, sex, nationality, occupational history, karnofsky score, pulmonary function related disease, smoking, alcoholic drinking history and eating habits; time of first diagnosis, the first symptoms, tumor location, histological type, diagnosis and TNM staging, treatment options, TPS physical parameters, blood and tumor markers and so on.Kaplan-Meier analysis was used to analysis the median time of one year's complication at the 54 patients.Elisa was used to detect the expression of MMP-9 and TIMP-1 with an empty stomach venous blood before(0Gy), during(40Gy), after(over 54Gy) the radiotherapy.100 7 to 8 weeks health SPF BALB/cmice were randomly divided into control group, 15 Gy irradiated group, 30 Gy irradiated group and GSH was used as preventive medicine for 15 Gy and 30 Gy irradiated mice. Mice were separated into 5 groups and 20 for each group. 0.2m L, 0.5% sodium pentobarbital was used to anesthesia the mice through intraperitoneal injection 5min before irradiation. 2min after anesthesia, GSH intervention group were intraperitioneal injected with 0.2m L, 240mg/m L. At the same time, and for controlling, the nonintervention group and blank group were injected with 0.2ml sodium with same operation.Fixed mouse, in the medial linear accelerator 6Mv X-ray, set1x2cm2 radiation field, and establish RILI experimental animal models. RILI experimental mice animal model was judged by biopsy of lung tissue and HE staining after 1 week irradiation.Experimental samples that contain blood, lung, were collected before irradiation and 1, 2, 3 weeks after irradiation. Blood that one of 100 u L was to measure blood routine at fully automatic blood analyzer was immediately centrifuged by 5000 r, 10 min and stored in-800 C for future test. ELISA used to detect the expression levels of MMP-9, TIMP-1. The pathological change in lung tissue was been observed after 10% formaldehyde, soak, dehydration, fixed, slice and HE staining. For immune level of RILI mice been observed. AVONA was applied to analysis mice activity, weight, blood, and expressions of MMP-9, TIMP-1at different times after different dose.Results:After 54 cases of lung cancer patients first time receiving radiation therapy, RILI incidence rate was 42.59 %, 1-2 grade 16 cases(29.6 %), 3-4 grade 7 cases(13.0 %). Age, gender, histological type, lesion location, treatment, KPS score, smoking, COPD has nothing to do with RILI, while it is related with V2 O, MLD, radiation dose and other physical parameters(P< 0.05). Blood picture will decline in the short term after radiotherapy, then rising and keep stable. After the influence factors of the ?2test meaningful of single factor, Multiariable Logistic analysis found treatment process with pneumonia and V20?25% was the independent affecting factors on RILI risk factors(P< 0.05) and the Logistic model with Y=-15.58+2.71X3+4.35X5. The difference was statistically significant(?2 = 5.78,P = 0.02)with RILI group of patients with median complicationtime was 8.7 months, and non-RILI group(median complication time = 9.9 months) after 1 year follow-up.Expression of MMP-9, TIMP-1 was significant different at different radiation doses(P< 0.05). There was statistic significance about un-RILI with high expression of MMP-9 after over radiotherapy(P< 0.05).Blank control group alveolar structure was clear, complete and not been seen obvious exudation, inflammatory cell infiltrate, but, 1 week after irradiation, it was been catch a large number of inflammatory cells infiltration in the lung tissue of mice with alveolar interval edema, hemorrhage, and structure was not complete, it was success of establishing RILI experimental mice animal model.After pure radiation, there was significant of degree of mouse activity, white blood cells, platelets, hemoglobin, and TIMP-1 decreased compared with blank group(P< 0.05), while, the expression of MMP-6 was increased(P < 0.05). The mice lung tissue injury with 30 Gy dose was exacerbate and serious, and was significant of every target compared with 15 Gy dose radiation(P< 0.05).As irradiation time increases, white blood cells, platelets, hemoglobin, TIMP-1were increased, however, MMP-9was decreased, there was significant compared with non-irradiation status(P<0.05).Lung tissue showed a large number of inflammatory cell infiltrations with alveolar septum edema, hemorrhage, alveolar wall injury and incomplete compared with blank group. After such irritation, inflammation, edema, hemorrhage of lung tissue was absorbed, much more clearly and complete in the third week than first week.Mice' RILI was significantly reduced after using GSH drugs for intervention. At the same dose, the GSH group of lung injury in mice was significantly reduced relatively compared with simple group, and GSH control function was stronger at low dose irradiation.Conclusions:Expression level of MMP-9 and TIMP-1 is increased with the increase of radiation dose, radiation size, and could been used as an important predictor of RILI incidence risk factors before radiation therapy. |
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