文献类型：期刊文献

中文题名：基于HIF-1信号通路探讨红芪多糖防治放射性肺炎的作用机制

英文题名：Mechanism of Hedysarum polybotrys Polysaccharides in the Prevention and Treatment of Radiation Pneumonia Based on HIF-1 Signaling Pathway

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

第一作者：王艺

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

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2023

卷号：39

期号：4

起止页码：46

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：甘肃省中医药研究中心专项开放课题(编号:zyzx-2020-zx19)。

语种：中文

中文关键词：红芪多糖;放射性肺炎;氧化损伤;缺氧诱导因子-1α信号通路

外文关键词：Hedysarum polybotrys polysaccharides;Radiation pneumonia;Oxidative damage;HIF-1 signaling pathway

摘要：目的:探讨红芪多糖防治急性放射性肺炎(Radiation pneumonitis, RP)的作用及机制。方法:小鼠分为正常对照组、模型对照组、红芪水煎液5 g/kg组、红芪多糖15、30和60 mg/kg组、阳性药吡非尼酮200 mg/kg组,各给药组预防性灌胃给药7 d后通过单次16 GyX线照射小鼠全胸部建立急性放射性肺炎模型,并继续给药至造模后3 d。分别在照射后第1、3 d药后30 min后处死小鼠8只,HE染色观察肺组织病理形态学变化;采用Western blot法检测肺组织中肿瘤坏死因子-α(TNF-α)、哺乳动物雷帕霉素靶蛋白(mTOR)、血管内皮生长因子(VEGF)及缺氧诱导因子-1α(HIF-1α)的蛋白表达,通过qRT-PCR法检测肺组织中Mtor、Vegf及Hif1a的mRNA表达,ELISA法检测血清中TNF-α、IL-6、SOD、GSH-Px及MDA的含量。结果:与正常对照组相比,RP模型对照组小鼠血清中TNF-α、IL-6及MDA含量升高,SOD、GSH-Px活力降低,肺组织中Mtor、Hif1a、Vegf的mRNA、蛋白表达明显上调(P<0.05或P<0.01);与模型对照组相比,各受试药物组小鼠血清中TNF-α、IL-6、MDA含量降低,SOD、GSH-Px活力升高;肺组织中TNF-α、mTOR、HIF-1α和VEGF的蛋白及mRNA表达下调(P<0.05或P<0.01),红芪多糖可改善RP小鼠的精神状态、皮毛光泽,降低肺系数,改善RP小鼠肺脏组织炎性反应。结论:红芪多糖防治急性放射性肺炎的发生和发展,与抑制HIF-1信号通路、氧化应激反应密切相关。
Objective:To investigate the effect of Hedysarum polybotrys polysaccharides on the prevention and treatment of acute radiation pneumonia(RP)and the mechanism.Methods:Mice were randomly divided into a control group,a model group,a 5 g/kg H.polybotrys water decoction group,15 mg/kg,30 mg/kg,and 60 mg/kg H.polybotrys polysaccharide groups,and a 200 mg/kg pirfenidone(positive drug)group.After 7 days of oral administration,acute RP model was established by irradiating the whole chest of mice with a single 16 GyX-ray,and the administration was continued until the 3rd day after modeling.On the 1st and 3rd days after irradiation,8 mice in each group were sacrificed 30 min after administration,respectively.The hematoxylin-eosin(HE)staining was used to observe the pathological changes in lung tissues,and Western blot was used to detect the protein expression levels of tumor necrosis factor-α(TNF-α),mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and hypoxia-inducible factor-1α(HIF-1α)in lung tissues.The mRNA expression levels of mtor,Vegf,and Hif-1αin lung tissues were detected by real-time quantitative polymerase chain(qRT-PCR),while the serum content of TNF-α,interleukin-6(IL-6),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected by the enzyme-linked immunosorbent assay(ELISA).Results:As compared with the control group,the serum content of TNF-α,IL-6,and MDA of the mice in the RP model group was increased.The activities of SOD and GSH-Px were decreased,and the mRNA and protein expression levels of mtor,Hif-1αand Vegf in the lung tissue were up-regulated in the RP model group.H.polybotrys polysaccharides improved the mental state and fur luster of mice with RP to a certain extent.The lung coefficient was reduced,and the inflammatory response of lung tissues was improved.Compared with the model group,the serum levels of TNF-α,IL-6,and MDA were reduced in each test drug group,and the activities of SOD and GSH-Px were increased.In the lung tissue,the mRNA expression levels of mtor,Hif-1α,and Vegf and the protein expression levels of TNF-α,mTOR,HIF-1α,and VEGF were down-regulated.Conclusion:H.polybotrys polysaccharides can prevent the occurrence and development of acute RP by inhibiting the HIF-1 signaling pathway,which is closely related to oxidative stress.