目的 研究红芪多糖对放射性肺损伤（radiation-induced lung injury，RILI）的防治作用及其机制。方法 雌性C57BL/6J小鼠随机分为对照组、模型组、红芪水煎液（5 g/kg）组及红芪多糖低、中、高剂量（15、30、60 mg/kg）组和吡非尼酮（200 mg/kg）组，每组8只。对照组佯装辐照，其余各组均采用单次16 Gy全肺X线辐照建立RILI模型。自造模前7 d，各给药组ig相应药物，1次/d，连续5周。所有小鼠均在取材前1 d进行肺功能检测；分别在造模前1 d及肺功能检测后进行CT影像学检测；采用苏木素-伊红（HE）染色观察小鼠肺组织病理变化；采用ELISA检测小鼠血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-6（interleukin-6，IL-6）水平；采用Western blotting检测小鼠肺组织中哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）、缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）、血管内皮生长因子（vascular endothelial growth factor，VEGF）及TNF-α蛋白表达。结果 与对照组比较，模型组小鼠肺泡炎症明显，肺功能受损，肺部CT值升高（P<0.01），血清中TNF-α及IL-6水平升高（P<0.01），肺组织中mTOR、HIF-1α、VEGF及TNF-α蛋白表达上调（P<0.01）。与模型组比较，红芪多糖组明显减轻小鼠肺泡炎症，改善肺功能，降低肺部CT值（P<0.01），抑制血清中TNF-α及IL-6水平（P<0.05、0.01），下调肺组织中mTOR、HIF-1α、VEGF及TNF-α蛋白表达（P<0.05、0.01）。结论 红芪多糖能够减轻小鼠RILI前期炎症的损伤，其机制可能与抑制mTOR/HIF-1α/VEGF信号通路有关。

Objective To investigate the preventive effect and mechanism of hedysarum polysaccharides on radiation-induced lung injury (RILI). Methods Female C57BL/6J mice were randomly divided into control group, model group, Hedysarum polybotrys decoction (5 g/kg) group, hedysarum polysaccharides low-, medium-, high-dose (15, 30, 60 mg/kg) groups and pirfenidone (200 mg/kg) group, with eight mice in each group. Control group was feigned to be irradiated, other groups were accepted a single dose of 16 Gy X-ray irradiation to establish RILI model. Before 7 d of modeling, each administration group was ig corresponding drugs, once a day for five weeks. All mice were tested for pulmonary function at 1 d before sampling; CT imaging was performed before modeling and after pulmonary function test; Hematoxylin-eosin (HE) staining was used to observe the pathological changes in lung tissue of mice; ELISA was used to detect levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum of mice; Western blotting was used to detect mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and TNF-α protein expressions in lung tissue of mice. Results Compared with control group, model group showed significant alveolar inflammation, impaired pulmonary function, and lung CT value was increased (P < 0.01), TNF-α and IL-6 levels in serum were increased (P < 0.01), mTOR, HIF-1α, VEGF and TNF-α protein expressions in lung tissue were up-regulated (P < 0.01). Compared with model group, hedysarum polysaccharides group reduced alveolar inflammation, improved pulmonary function, reduced lung CT value (P < 0.01), inhibited levels of TNF-α and IL-6 in serum (P < 0.05, 0.01), and down-regulated mTOR, HIF-1α, VEGF and TNF-α protein expressions in lung tissues (P < 0.05, 0.01). Conclusion Hedysarum polysaccharides can effectively alleviate the inflammatory injury in early stage of RILI in mice, and its mechanism may be related to the inhibition of mTOR/HIF-1α/VEGF signaling pathway.

R285.5

甘肃省人才发展专项资金（40160401）；甘肃省中医药研究中心专项开放课题（zyzx-2020-zx19）