文献类型：期刊文献

中文题名：基于mTOR/HIF-1α/VEGF通路研究红芪多糖防治放射性肺损伤的作用机制

英文题名：Mechanism of hedysarum polysaccharides on preventing and treating radiation- induced lung injury based on mTOR/HIF-1a/VEGF signaling pathway

作者：王强[1];王艺[1];张莉[1];尚芸[1];李亮亮[1];杜芹[1];李爽[1];蔺兴遥[1,2]

第一作者：王强

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]敦煌医学与转化教育部重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2022

卷号：53

期号：21

起止页码：6771

中文期刊名：中草药

外文期刊名：Chinese Traditional and Herbal Drugs

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：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)。

语种：中文

中文关键词：红芪多糖;放射性肺损伤;肺功能;炎症;哺乳动物雷帕霉素靶蛋白/缺氧诱导因子-1α/血管内皮生长因子信号通路

外文关键词：hedysarum polysaccharides;radiation-induced lung injury;lung function;inflammation;mammalian target of rapamycin/hypoxia-inducible factor-1la/vascular endothelial growth factor signaling pathway

摘要：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-αprotein 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-αand IL-6 levels in serum were increased(P<0.01),mTOR,HIF-1α,VEGF and TNF-αprotein 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-αand IL-6 in serum(P<0.05,0.01),and down-regulated mTOR,HIF-1α,VEGF and TNF-αprotein 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.