中国现代医学杂志2018，Vol.28Issue(2)：26-32,7.DOI:10.3969/j.issn.1005-8982.2018.02.005
阿米福汀对小鼠放射性肺损伤的防护作用研究
Protective effect of Amifostine against radiation-induced lung injury in mice and its mechanism
摘要
Abstract
Objective To investigate the radioprotective function of Amifostine (AMI) in mice with acute radiation-induced lung injury and its mechanism. Methods Totally 24 female C57BL/6J mice were randomized into 3 groups as AMI group (treated by AMI 200 mg/kg plus radiation), radiation group and solvent control group. The mouse lungs in the radiation group and the AMI group were irradiated with linear accelerator 6MV X-ray at a single dose of 12 Gy, and those in the solvent control group received sham radiation. The mice in the AMI group were intraperitoneally injected with Amifostine 30 minutes before irradiation, while the same volume of solvent was given to the control and radiation groups. The mice were sacrified and the mouse lung tissue was collected 14 days after irradiation. The pathological changes in the lung tissue were observed after HE staining. The levels of IL-6, TNF-αand TGF-β1 in the bronchoalveolar lavage fluid (BALF) were measured by ELISA. The NF-κB activity was detected by EMSA. The expression and positioning of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) in the lung tissue were observed by immunohistochemical method. The expressions of NLRP3 and IL-1β mRNAs in the lung tissue were assayed by qRT-PCR. And the expressions of NF-κB p65, NLRP3 and IL-1βproteins in the lung tissue were assayed by Western blot. Results On the 14th day after irradiation, compared with the radiation group, acute inflammatory reaction of the lung tissue was alleviated, the IL-6 and TNF-α levels in BALF were markedly decreased (P < 0.05), the level of TGF-β1 in BALF rose slightly (P < 0.05), and NF-κB activity in the lung tissue was obviously reduced (P < 0.05) in the AMI group. Immunohistochemical results showed that the expressions of NLRP3 and IL-1β mRNAs were obviously reduced (P < 0.05), and the expressions of NF-κB p65, NLRP3 and IL-1β proteins in the lung tissue were obviously reduced (P < 0.05) in the AMI group compared to the radiation group. Conclusions Amifostine can down-regulate the activitity of NF–κB, then inhibit transcription and expression of NLRP3 gene and effectively reduce the release of inflammatory cytokines, therefore alleviate acute radiation-induced lung injury in mice.关键词
阿米福汀/放射性肺损伤/NF-κB/NLRP3/白介素-1βKey words
Amifostine/radiation-induced lung injury/nucleotide-binding domain and leucine-rich repeat containing proteins/nuclear factor-κB/interleukin-1β分类
医药卫生引用本文复制引用
宣伟,李帅,吴秀艳,耿艳,张卓..阿米福汀对小鼠放射性肺损伤的防护作用研究[J].中国现代医学杂志,2018,28(2):26-32,7.基金项目
辽宁省科学技术计划项目(No:2014225003) （No:2014225003）
