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Objective::To observe the effect of compound Kushen injection on the expressions of transforming growth factor-β1 (TGF-β1), drosophila mothers against decapentaplegic protein 3 (Smad3), glycogen synthase kinase-3β (GSK-3β) and β-catenin mice models with radiation-induced pulmonary injury (RIPI), in order to explore its possible mechanism of action. Method::On XStrahl precision radiation research platform for small animals (SARRP), a single 20 Gy bilateral lung field irradiation was performed to establish a mice model of RIPI. Thirty-two mice were randomly divided into normal control group, model group, compound Kushen injection group and dexamethasone injection group. The normal control group and the model group were given an equal volume of 0.9%sodium chloride solution and injected intraperitoneally for 4 weeks. The pathology of lung tissue tissues was observed by using hematoxylin-eosin (HE) staining. Immunohistochemical(IHC) was used to detect the expressions of E-cadheren and Vimentin proteins in mice lung tissues.Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expressions of TGF-β1, Smad3, GSK-3β and β-cateninin.Western blot was used to detect the protein expressions of TGF-β1, Smad3, GSK-3β and β-cateninin. Result::Compared with the normal group, the pulmonary coefficient of the model group was significantly decreased (P<0.01). Inflammatory cell infiltration, pulmonary interstitial edema, congestion, destruction of alveolar structure and partial alveolar atrophy were observed in the lung tissues of the model group. Compared with the model group, in the compound Kushen injection group, the levels of infiltration of lung inflammatory cells and pulmonary interstitial lesions in mice, the expression of Vimentin in lung tissues (P<0.01), and the expressions of TGF-β1, Smad3, GSK-3β and β-cateninin were significantly decreased (P<0.01), whereas the expression of E-cadheren was significantly increased (P<0.01). However, compared with the dexamethasone injection group, in the compound Kushen injection group, the pathological changes of lung tissues were similar, and the expression levels of E-cadheren, Vimentin, TGF-β1, Smad3, GSK-3β and β-cateninin were not significantly different. Conclusion::Compound Kushen injection can alleviate pulmonary fibrosis of lung in the treatment of RIPI, and the mechanism may be associated with inhibiting the mRNA and protein expressions of TGF-β1, Smad3, GSK-3β and β-catenin related to epithelial-mesenchymal transition(EMT), promoting the expression of E-cadheren, and inhibiting the expression of Vimentin, so as to inhibit the occurrence of EMT.
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OBJECTIVE: To discuss the effect of Qingfei-yangyin-huoxue recipe on radiation-induced pulmonary injury by regulating the lncRNA NANCI-NKX2.1 pathway. METHODS: The C57BL/6 mice were randomly divided into normal control group (A group, n=16), drug only group (B group, n=16), model group (C group, n=16) and drug model group (D group, n=16). After exposure to Qingfei-yangyin-huoxue recipe for 10 w, the pathological change of lung tissue was examined by H&E and Masson staining. The expressions of lncRNA NANCI and NKX2.1 mRNA in lung tissues were detected by qRT-PCR. And the NKX2.1 protein expressions were detected by Western blot. RESULTS: The mean animal weight in D groups was less than A and B group, but more than C group after treatment of 7 d(P<0.05). There were marked interstitial edema and inflammatory cells, fibrocytes accumulation in C group but not in A and B groups by H&E and Masson stain. The alveolitis and fibrosis changes in D group were better than C group. And the mean radiation-induced pulmonary injury score in D group was (3.875±1.746), which was less than C group, but more than A and B groups (P<0.05). The expression of lncRNA NANCI and NKX2.1in D group was higher than C group, but lower than A and B groups (P<0.05). Besides, the radiation-induced pulmonary injury score was negative related with lncRNA NANCI and NKX2.1 (r=-0.510, -0.786, P<0.05). CONCLUSION: There are significant evidences that Qingfei-yangyin-huoxue recipe could protect radiation-induced pulmonary injury by up-regulation lncRNA NANCI-NKX2.1 pathway.
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Objective To evaluate the radioprotective effects of metformin on radiation-induced pulmonary injury in rats. Method A total of 30 Sprague-Dawley ( SD) rats were randomly divided into three groups:control, radiation (20 Gy) and radiation (20 Gy) with metformin, with 10 rats in each group. The right lungs of rats were irradiated to 20 Gy with 6 MV X-rays. Computed tomography (CT) was performed and Hounsfield Units ( HU) were determined during the observation period. The tissue samples of lung were extracted to perform the histological analysis, measurement of hydroxyproline content, fibrosis score and evaluation of fibrosis/inflammatory markers by Western blot at 12 weeks post-irradiation. CCK-8 method was used to explore the effects of metformin on non-small cell lung cancer( NSCLC) cells A549 and H460. Results Metformin reduced radiologic and histologic signs of fibrosis, lung density(6. 52 ± 0. 43 vs. 3. 31 ± 0. 57, t=6. 37, P<0. 01) and hydroxyproline content(32. 58 ± 1. 59 vs. 23. 47 ± 2. 46,t=12. 72, P<0. 01) which had been increased due to irradiation. Meanwhile, it significantly decreased the expressions of Col1, p-AMPKα and TGF-β, while inhibited the expressions of p-Smad2 and p-Smad3 compared to the irradiation alone group. Moreover, metformin reduced A549 and H460 cells growth. Conclusions Metformin exerted a protective effect on normal tissues in radiation-induced pulmonary fibrosis. Thus, it might act as a promising radioprotective agent in the treatment of lung cancer.
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Radiation-induced pulmonary injury(RPI)refers to intrathoracic neoplasm after radiotherapy, radiation wild area normal lung tissue injury complicated by damage to the reaction. Traditional Chinese medicine was used for nourishing yin and clearing lung, heat-clearing and detoxifying, promoting blood circulation to remove blood stasis in reducing the adverse reaction of radiotherapy. TCM showed the advantage for radioactive lung injury. Based on the different mechanism of action and from the perspective of TCM treatment, the article reviewed the latest experiment research of TCM on radiation-induced pulmonary injury were summarized, and we discussed and pointed out the existing problems and prospect solution
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Objective To evaluate the radioprotective effects of metformin on radiation-induced pulmonary injury in rats. Method A total of 30 Sprague-Dawley ( SD) rats were randomly divided into three groups:control, radiation (20 Gy) and radiation (20 Gy) with metformin, with 10 rats in each group. The right lungs of rats were irradiated to 20 Gy with 6 MV X-rays. Computed tomography (CT) was performed and Hounsfield Units ( HU) were determined during the observation period. The tissue samples of lung were extracted to perform the histological analysis, measurement of hydroxyproline content, fibrosis score and evaluation of fibrosis/inflammatory markers by Western blot at 12 weeks post-irradiation. CCK-8 method was used to explore the effects of metformin on non-small cell lung cancer( NSCLC) cells A549 and H460. Results Metformin reduced radiologic and histologic signs of fibrosis, lung density(6. 52 ± 0. 43 vs. 3. 31 ± 0. 57, t=6. 37, P<0. 01) and hydroxyproline content(32. 58 ± 1. 59 vs. 23. 47 ± 2. 46,t=12. 72, P<0. 01) which had been increased due to irradiation. Meanwhile, it significantly decreased the expressions of Col1, p-AMPKα and TGF-β, while inhibited the expressions of p-Smad2 and p-Smad3 compared to the irradiation alone group. Moreover, metformin reduced A549 and H460 cells growth. Conclusions Metformin exerted a protective effect on normal tissues in radiation-induced pulmonary fibrosis. Thus, it might act as a promising radioprotective agent in the treatment of lung cancer.
ABSTRACT
Radiation-induced pulmonary injury(RPI)refers to intrathoracic neoplasm after radiotherapy, radiation wild area normal lung tissue injury complicated by damage to the reaction. Traditional Chinese medicine was used for nourishing yin and clearing lung, heat-clearing and detoxifying, promoting blood circulation to remove blood stasis in reducing the adverse reaction of radiotherapy. TCM showed the advantage for radioactive lung injury. Based on the different mechanism of action and from the perspective of TCM treatment, the article reviewed the latest experiment research of TCM on radiation-induced pulmonary injury were summarized, and we discussed and pointed out the existing problems and prospect solution