盐酸青藤碱对支气管哮喘小鼠Nrf2/HO-1信号通路的影响  

Effect of sinomenine hydrochloride on Nrf2/HO-1 signaling pathway in bronchial asthma mice

作　　者：朱丽萍 赵红玉 邓艳 王荣丽 

机构地区：[1]西南医科大学附属医院呼吸与危重症医学科,四川泸州646000

出　　处：《临床肺科杂志》2024年第9期1373-1379,共7页Journal of Clinical Pulmonary Medicine

基　　金：四川省科技计划项目(No.2020YFS0003)。

摘　　要：目的 探讨盐酸青藤碱(SH)对卵清蛋白(OVA)诱导的支气管哮喘小鼠气道炎症及氧化应激的作用及其可能机制。方法 将40只Balb/c小鼠随机分为对照组(PBS组)、哮喘模型组(BA组)、SH低、中和高剂量实验组(SH-L、M、H,40、80、160mg/kg),各8只。采取OVA腹腔注射法制备小鼠哮喘模型。以HE染色和PAS染色检测各组小鼠肺组织病理变化和黏液分泌水平,以ELISA法检测各组小鼠血清中白细胞介素-5(IL-5)、白细胞介素-13(IL-13)、肿瘤坏死因子-α(TNF-α)和免疫球蛋白E(IgE)含量,以超氧化物歧化酶(SOD)、丙二醛(MDA)和还原型谷胱甘肽(GSH)试剂盒检测各组小鼠肺组织中SOD、MDA和GSH含量,以Western Blot法和qRT-PCR法分别检测各组小鼠肺组织中核转录因子E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)的蛋白和mRNA表达水平。结果 与PBS组比较,BA组小鼠肺组织见气管壁增厚,周围大量炎症细胞浸润,杯状细胞增生等病理学表现,IL-5、IL-13、TNF-α和IgE含量、MDA含量、Nrf2和HO-1蛋白和mRNA表达水平升高(P<0.05),SOD和GSH含量显著下降(P<0.001);与BA组比较,SH-L、M、H组肺组织病理学变化均有好转,IL-5、IL-13、TNF-α和IgE含量、MDA含量下降,SOD和GSH含量、Nrf2和HO-1蛋白和mRNA表达水平升高,以SH-H组效果最佳(P<0.05)。结论 SH能够改善哮喘小鼠肺组织氧化应激反应,减轻哮喘小鼠气道炎症,其机制可能与SH增强Nrf2/HO-1信号通路有关。Objective To investigate the effect and its possible mechanism of sinomenine hydrochloride(SH)on airway inflammation and oxidative stress induced by ovalbumin(OVA)in bronchial asthma mice.Methods Forty Balb/c mice were randomly divided into a control group(PBS group),asthma model group(BA group),SH low-dose,medium-dose,and high-dose experimental group(SH-L,M,H,40、80、160mg/kg)(n=8 each).The mouse asthma model was prepared by OVA intraperitoneal injection.HE staining and PAS staining were used to detect the pathological changes of lung tissue and the level of mucus secretion,ELISA was used to detect the contents of interleukin-5(IL-5),interleukin-13(IL-13),tumor necrosis factor(TNF-α)and immunoglobulin E(IgE)in serum and lung tissues.Superoxide dismutase(SOD),malondialdehyde(MDA),and reduced glutathione(GSH)detection kits were used to detect the SOD,MDA,and GSH contents in lung tissues of mice,the protein and mRNA expressions of nuclear transcription factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in lung tissue were detected by Western Blot and qRT-PCR.Results Compared with the PBS group,the pulmonary tissue of the BA group showed pathological changes such as the thickness of airway wall and infiltration of a large number of surrounding inflammatory cells,the IL-5,IL-13,TNF-α,and IgE contents,MDA contents,Nrf2 and HO-1 protein and mRNA expression were higher(P<0.05),the contents of SOD and GSH were significantly decreased(P<0.001).Compared with the BA group,the pathological changes of the lung in the SH-L,M,and H group were improved,the IL-5,IL-13,TNF-αand IgE contents,MDA contents were decreased,SOD and GSH contents,Nrf2 and HO-1 protein and mRNA expression were increased,SH-H group had the best effect(P<0.05).Conclusion SH can improve oxidative stress in the lung tissue of asthmatic mice,and reduce airway inflammation,and the mechanism may be related to the enhancement of the Nrf2/HO-1 signaling pathway.

关 键 词：盐酸青藤碱 支气管哮喘 氧化应激 Nrf2/HO-1信号通路 

分 类 号：R285.5[医药卫生—中药学]