摘要
目的:探究加味补肺汤是否通过Nrf2-Keap1通路发挥对博来霉素(BLM)诱导的肺纤维化(IPF)大鼠的治疗作用。方法:气管滴注BLM构建IPF大鼠模型。造模成功大鼠分为模型对照、吡非尼酮0.07 g/kg、加味补肺汤7.5、15、30 g/kg组,另设正常对照组,每组6只,连续灌胃给予相应药物或生理盐水,4 w后检测呼吸功能,观察肺组织的炎症程度和纤维化程度的改变及血清超氧化物歧化酶(SOD)和丙二醛(MDA)活性或含量的改变,检测白介素1β(IL-1β)、IL-6的含量;免疫组化法检测肺内Nrf2和Keap1的蛋白表达。结果:与正常对照组相比,模型对照组吸气时间、呼气时间明显增加,潮气量明显降低,肺组织炎症程度,胶原增殖显著升高(P<0.05或P<0.01),血清IL-1β、IL-6、MDA的含量及肺组织Keap1表达明显升高(P<0.05或P<0.01),血清SOD活力、Nrf2蛋白表达明显降低(P<0.05或P<0.01);与模型对照组相比,加味补肺汤各组吸气时间、呼气时间明显降低,潮气量明显增加,肺组织炎症评分,胶原增殖评分明显降低(P<0.05或P<0.01),血清IL-1β、IL-6、MDA的含量及肺组织Keap1蛋白表达明显降低(P<0.01),血清SOD活力、肺组织Nrf2蛋白表达明显升高(P<0.01)。结论:加味补肺汤通过调控Nrf2-Keap1信号通路,能够显著降低大鼠肺组织的氧化应激损伤和炎症反应程度,改善大鼠特发性肺纤维化进程。
Objective:To investigate whether Jiawei Bufei Decoction(加味补肺汤)exerts a therapeutic effect on the lung tissue of rats with bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF)through the nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1(Nrf2-Keap1)signaling pathway.Methods:BLM was infused into the trachea of rats to induce an IPF model.After successful modeling,rats were randomly divided into a normal control group,a model control group,a pirfenidone 0.07 g/kg group,and three Jiawei Bufei Decoction treatment groups(7.5,15,and 30 g/kg),with 6 rats in each group.All rats were administrated with corresponding drugs or saline water.After 4 w,the respiratory function was detected,and the changes of inflammation and fibrosis in the lung tissues,and the serum content of superoxide dismutase(SOD)and malondialdehyde(MDA)were observed.The content of interleukin 1β(IL1β)and interleukin 6(IL6)were detected.The protein expressions of Nrf2 and Keap1 were determined by immunohistochemistry.Results:As compared with the normal control group,the inspiration and exhalation time was significantly prolonged in the model group,the tidal volume was decreased,and the score of lung inflammation and collagen proliferation was increased(P<0.05 or P<0.01).The content of IL1β,IL6,MDA,and Keap1 in the model group was increased(P<0.05 or P<0.01),while that of SOD and Nrf2 was significantly decreased(P<0.05 or P<0.01).Compared with the model group,the inspiration and exhalation time was significantly reduced,the tidal volume was increased,and the score of lung inflammation and collagen proliferation was significantly decreased(P<0.05 or P<0.01)in the Jiawei Bufei Decoction groups.The content of IL1β,IL6,MDA,and Keap1 in the Jiawei Bufei Decoction groups were significantly decreased(P<0.01),while the SOD activity and protein expression of Nrf2 was significantly increased(P<0.01).Conclusion:Jiawei Bufei Decoction reduces oxidative stress injury and inflammatory reaction in the lung tissue of rats by regulating the Nrf2-Keap1 signaling pathway,thus improving the process of IPF in rats.
作者
赵梦雅
刘杨
姜梦笔
张浩宇
黄高
陈蕾蕾
Zhao Mengya;Liu Yang;Jiang Mengbi;Zhang Haoyu;Huang Gao;Chen Leilei(Guizhou University of Traditional Chinese Medicine,Guiyang 550025;Guangzhou University of Chinese Medicine,Guangzhou 510006)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2022年第3期48-52,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
贵州省科技计划项目(黔科合基础[2020]1Y384)
关键词
加味补肺汤
特发性肺纤维化
炎症反应
氧化应激
转录因子NF-E2相关因子2-Kelch样ECH相关蛋白1信号通路
Jiawei Bufei Decoction(加味补肺汤)
idiopathic pulmonary fibrosis
inflammatory reaction
oxidative stress
nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1(Nrf2-Keap1)signaling pathway
作者简介
通信作者:陈蕾蕾,博士,教授,研究方向:从事中医文献学研究,E-mail:29671693@qq.com;赵梦雅,硕士研究生,研究方向:从事中医学基础方面研究,E-mail:2390701481@qq.com。
