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虾青素对小鼠放射性肺纤维化的防治作用
赵德云,雷霄,赵海男,郭佳铭,曲红金,杨彦勇,张沛,程赢,刘聪,崔建国,高福,蔡建明,李百龙*
0
(第二军医大学海军医学系舰船辐射医学教研室, 上海 200433
共同第一作者
*通信作者)
摘要:
目的 探讨虾青素对小鼠放射性肺纤维化的防治作用及其机制。方法 60只雌性C57BL/6小鼠随机分为正常组、照射组、照射+虾青素组(25 mg/kg),每组20只。除正常组外,其余各组均以60Co γ射线单次16 Gy全胸照射,照射+虾青素组在照射前后每天1次灌胃各7 d。照射后1、4、8、16周处死小鼠,取肺组织进行Masson染色,检测肺组织中超氧化物歧化酶(superoxide dismutase, SOD)活性、丙二醛(malondialdehyde, MDA)含量和羟脯氨酸(hydroxyproline, Hyp)含量,测定血清中转化生长因子β1(transforming growth factor-beta 1, TGF-β1)含量。结果 小鼠受照射后肺纤维化严重程度随照后时间延长而加重,用虾青素处理后可明显减轻小鼠肺纤维化严重程度,提高肺组织SOD活力(P<0.05或P<0.01)并减少脂质过氧化产物MDA含量(P<0.05或P<0.01);抑制小鼠肺组织Hyp和血清中TGF-β1含量的升高(P<0.05或P<0.01)。结论 虾青素能够有效地减轻放射性肺纤维化,其机制可能与虾青素能够提高机体的抗氧化能力、下调促纤维化因子TGF-β1表达有关。
关键词:  辐射损伤  肺纤维化  虾青素  抗氧化剂  转化生长因子β1
DOI:10.16781/j.0258-879x.2016.04.0446
投稿时间:2015-11-13修订日期:2016-01-05
基金项目:上海市自然科学(No.14ZR1449200).Supported by Natural Science Foundation of Shanghai (No.14ZR1449200)
Protective effect of astaxanthin against radiation-induced lung fibrosis in mice
ZHAO De-yun,LEI Xiao,ZHAO Hai-nan,GUO Jia-ming,QU Hong-jin,YANG Yan-yong,ZHANG Pei,CHENG Ying,LIU Cong,CUI Jian-guo,GAO Fu,CAI Jian-ming,LI Bai-long*
(Department of Marine Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China
Co-first authors
*Corresponding author)
Abstract:
Objective To evaluate the effect of astaxanthin against radiation-induced lung fibrosis in mouse model and to investigate the underlying mechanism. Methods A total of 60 female C57BL/6 mice were evenly randomized into control group, model group (IR) and astaxanthin-treated group (IR+AST). Mouse models of radiation-induced lung fibrosis were generated by thoracic irradiation with a single dose of 16 Gy. Mice in IR+AST group were orally administrated with astaxanthin (25 mg/kg) daily for 7 days both before and after irradiation. Then the mice were sacrificed at 1, 4, 8 and 16 weeks after radiation, and the lung samples were collected in each group for morphological observation. The severity of fibrosis was evaluated by Masson's trichrome after radiation. The oxidative stress was determined by malondialdehyde (MDA) and superoxide dismutase (SOD) assay kit, the collagen deposition was measured by hydroxyproline (Hyp) assay kit, and the serum level of transforming growth factor-beta 1(TGF-β1) was measured by ELISA. Results Pathological staining results showed that the pulmonary fibrosis became more severe along with time increase after irradiation, and astaxanthin attenuated the fibrosis formation. Compared with irradiation model group, the MDA level in IR+AST group was significantly lower (P<0.05 or P<0.01) and SOD level was significantly higher (P<0.05 or P<0.01) at different time points. Radiation increased the serum TGF-β1 and Hyp content in lung tissue at 4, 8 and 16 weeks post irradiation, and astaxanthin significantly reduced TGF-β1 and Hyp contents (P<0.05 or P<0.01)). Conclusion Astaxanthin can effectively alleviate radiation-induced lung fibrosis (RILF), which is probably via inhibition of TGF-β1 expression and reduction of lipid peroxidation injury.
Key words:  radiation-injuries  pulmonary lung fibrosis  astaxanthin  antioxidants  transforming growth factor β1