黄根多糖激活Nrf2对博来霉素致小鼠肺纤维化的保护作用  

Protective effect of polysaccharide of Prismatomeria tetrandra in activating Nrf2 against bleomycin-induced pulmonary fibrosis in mice

作　　者：欧阳怡佩 黄艳 郑凯 姚鸿飞 黄世稳 OUYANG Yipei;HUANG Yan;ZHENG Kai;YAO Hongfei;HUANG Shiwen(School of Basic Medical Sciences,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China)

机构地区：[1]右江民族医学院基础医学院,广西百色533000

出　　处：《右江民族医学院学报》2024年第3期336-342,共7页Journal of Youjiang Medical University for Nationalities

基　　金：广西壮族自治区研究生教育创新计划项目(YCSW2023504)。

摘　　要：目的探讨黄根多糖(polysaccharide of Prismatomeria tetrandra,PSPT)是否通过激活Nrf2发挥抗肺纤维化(Pulmonary fibrosis,PF)作用。方法通过气管内滴注博来霉素(Bleomycin,BLM)创建小鼠肺纤维化模型,随机分为对照组,BLM组,PSPT低、中、高(40 mg/kg、100 mg/kg、250 mg/kg)剂量组,吡非尼酮(Pirfenidone,PFD)组(200 mg/kg),分别根据小鼠体重灌胃给药或等量的生理盐水,给药28 d后取肺组织标本,H&E、Masson染色检测肺纤维化程度;碱水解法测定肺组织中羟脯氨酸(HYP)水平;RT-qPCR及免疫荧光法检测肺组织中Nrf2的mRNA及蛋白表达水平。结果与对照组比较,模型组肺组织损伤及纤维化显著。与模型组比较,PSPT各剂量组及PFD组炎症反应及纤维化影响有所减轻;各给药组HYP水平显著降低(P<0.001);PSPT中、高剂量组Nrf2的mRNA水平明显升高(P<0.01);PSPT高剂量组Nrf2转录因子蛋白水平显著提高(P<0.001)。结论PSPT可能通过激活Nrf2表达来保护细胞免受氧化损伤,从而促进Nrf2在细胞核内的积累,增加抗氧化酶活性,进而通过Nrf2抑制氧化应激而发挥抗肺纤维化作用。Objective To investigate whether polysaccharide of Prismatomeria tetrandra(PSPT)exerts an anti-pulmonary fibrosis(PF)effect by activating nuclear factor erythrocyte 2-related factor 2(Nrf2).Methods A mouse lung fibrosis model was established by intratracheal instillation of bleomycin(BLM).The mice were randomly divided into a control group,a BLM model group,low(40 mg/kg),medium(100 mg/kg)and high(250 mg/kg)dose PSPT groups,and a pirfenidone(PFD)group(200 mg/kg)which were administered by gavage according to the body weights of the mice,or by an equal amount of physiological saline,respectively.Lung tissue specimens were collected after 28 days of drug administration,and H&E and Masson staining were used to detect the degree of lung fibrosis.hydroxyproline(HYP)level in lung tissue was determined by alkaline hydrolysis method,while RT-qPCR and immunofluorescence methods were employed to detect the mRNA and protein expression levels of Nrf2 in lung tissue,respectively.Results When compared with the control group,lung tissue damage and fibrosis were significant in the model group.In contrast,the inflammatory response and fibrosis were attenuated in all PSPT dose groups and the PFD group compared to the model group.Additionally,the HYP level was significantly decreased in each treatment group(P<0.001).The mRNA levels of Nrf2 were significantly increased in the middle and high-dose PSPT groups(P<0.01),while the protein level of the Nrf2 transcription factor was significantly elevated in the high-dose PSPT group(P<0.001).Conclusion PSPT may protect cells from oxidative damage by activating Nrf2 expression,thus promoting the accumulation of Nrf2 in the nucleus and increasing antioxidant enzyme activity.Consequently,PSPT exerts an anti-PF effect by inhibiting oxidative stress through Nrf2 pathway.

关 键 词：肺纤维化 博莱霉素 黄根多糖 

分 类 号：R563.13[医药卫生—呼吸系统]