Tang Fei, Li Rui, Xue Jianxin, Lan Jie, Xu He, Liu Yongmei, Zhou Lin, Lu You
Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Department of Medical Oncology, Guizhou Province People's Hospital, Guiyang, Guizhou 550002, P.R. China.
Oncol Lett. 2017 Nov;14(5):5211-5220. doi: 10.3892/ol.2017.6813. Epub 2017 Aug 24.
Radiation-induced lung injury (RILI) is a common and major obstacle in thoracic cancer radiotherapy, resulting in considerable morbidity and limiting the dose of radiation. However, an effective treatment option remains to be established. Therefore, the present study aimed to investigate the effects of azithromycin (AZM) in acute RILI with a mouse model. In the present study, C57BL/6 mice were given a single thoracic irradiation of 16 Gy and administered orally with AZM. The lung histopathological findings, the levels of malondialdehyde (MDA; an indicator of oxidative damage) and the concentration of pro-inflammatory and pro-fibrotic cytokines in plasma were assessed on 28 day following irradiation. In addition, the total cell counts in bronchoalveolar lavage fluid (BALF), the pro-inflammatory and pro-fibrotic cytokine gene expression in lung tissue were evaluated on day 7, 14 and 28 following irradiation. Administration with AZM markedly alleviated acute RILI as indicated by hematoxylin and eosin and Masson staining. The levels of MDA and total cell counts in BALF significantly reduced in AZM treated mice. AZM also down-regulated the concentration and mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1. In addition, AZM attenuated the irradiation-induced increases in the mRNA expression of fibrotic markers (α-smooth muscle actin and α-1 type I collagen). AZM treatment mitigated the radiation-induced acute lung injury possibly by its anti-inflammatory and anti-fibrotic effects.
放射性肺损伤(RILI)是胸段癌放疗中常见的主要障碍,会导致相当高的发病率并限制放疗剂量。然而,仍有待确立一种有效的治疗方案。因此,本研究旨在用小鼠模型探究阿奇霉素(AZM)对急性RILI的影响。在本研究中,给C57BL/6小鼠单次进行16 Gy的胸部照射,并口服给予AZM。在照射后第28天评估肺组织病理学结果、丙二醛(MDA;氧化损伤指标)水平以及血浆中促炎和促纤维化细胞因子的浓度。此外,在照射后第7、14和28天评估支气管肺泡灌洗液(BALF)中的总细胞计数以及肺组织中促炎和促纤维化细胞因子的基因表达。苏木精-伊红染色和Masson染色显示,给予AZM可显著减轻急性RILI。AZM处理的小鼠中,MDA水平和BALF中的总细胞计数显著降低。AZM还下调了白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α和转化生长因子-β1的浓度及mRNA表达。此外,AZM减弱了照射诱导的纤维化标志物(α-平滑肌肌动蛋白和α-1Ⅰ型胶原)mRNA表达的增加。AZM治疗可能通过其抗炎和抗纤维化作用减轻了辐射诱导的急性肺损伤。