五味子乙素调节Noxa/Hsp27/NF-κB信号通路对哮喘大鼠气道炎症和气道重塑的影响  

Impacts of Schisandrin B on airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Hsp27/NF-κB signaling pathway

作　　者：雷俊[1] 罗玲艳 乔松[1] LEI Jun;LUO Lingyan;QIAO Song(Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430000,China;School of Medicine,Yangtze University,Jingzhou 434000,China)

机构地区：[1]武汉市中医医院,武汉430000 [2]长江大学医学院,荆州434000

出　　处：《中国免疫学杂志》2024年第12期2484-2489,共6页Chinese Journal of Immunology

基　　金：武汉市医学科研项目(WZ21C57)。

摘　　要：目的:探讨五味子乙素(Sch B)调节Noxa/热休克蛋白27(Hsp27)/核因子-κB(NF-κB)信号通路对哮喘大鼠气道炎症和气道重塑的影响。方法:将SD雄性大鼠随机分为对照组(正常饲养)、哮喘组、Sch B-L组(40 mg/kg)、Sch B-H组(80 mg/kg)、阳性对照组(0.5 mg/kg地塞米松)、Vector组(尾静脉注射空载质粒^(+)80 mg/kg Sch B)、Noxa组(尾静脉注射Noxa过表达质粒^(+)80 mg/kg Sch B),每组6只。除对照组外,其余6组大鼠均采用卵清蛋白致敏和激发构建哮喘大鼠模型,给予药物干预,每天1次,干预4周。RT-qPCR检测肺组织Noxa表达;对支气管肺泡灌洗液(BALF)进行白细胞分类计数;ELISA测定血清IL-4、TNF-α、IL-13、IL-5水平;HE染色评估肺组织病理变化;Western blot测定肺组织Noxa蛋白表达及Hsp27、NF-κB磷酸化水平。结果:相较于Vector组,Noxa组大鼠左肺组织Noxa表达明显增加;与对照组相比,哮喘组大鼠右肺组织结构明显受损,气管管道明显出现狭窄现象,间质大量炎性浸润,支气管平滑肌厚度,基底膜厚度和基底膜周径显著增加,BALF中细胞总数、嗜酸性粒细胞、中性粒细胞、淋巴细胞明显增多,巨噬细胞明显减少,血清中TNF-α、IL-4、IL-5、IL-13的水平显著升高,左肺组织中Noxa、p-Hsp27/Hsp27、p-NF-κB p65/NF-κB p65表达水平显著升高(P<0.05);与哮喘组比较,Sch B-L组和Sch B-H组和阳性对照组大鼠右肺组织管道狭窄现象明显改善,炎症浸润减少,支气管平滑肌厚度,基底膜厚度和基底膜周径明显降低,BALF中细胞总数、嗜酸性粒细胞、中性粒细胞、淋巴细胞显著减少,巨噬细胞明显增多,血清中TNF-α、IL-4、IL-5、IL-13的水平显著降低,左肺组织中Noxa、p-Hsp27/Hsp27、p-NF-κB p65/NF-κB p65表达水平显著降低,且呈剂量依赖性(P<0.05);Noxa过表达后,减弱了Sch B对哮喘大鼠气道炎症和气道重塑的改善作用。结论:Sch B可通过调节Noxa/Hsp27/NF-κB信号通路有效改善哮喘大鼠的气�Objective:To investigate the impacts of Schisandrin B(Sch B)on airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Heat shock protein 27(Hsp27)/nuclear factor-κB(NF-κB)signaling pathway.Methods:SD male rats were randomly separated into control group(normal feeding),asthma group,Sch B-L group(40 mg/kg),Sch B-H group(80 mg/kg),positive control group(0.5 mg/kg dexamethasone),Vector group(tail vein injection of empty plasmid^(+)80 mg/kg Sch B),Noxa group(tail vein injection of Noxa overexpression plasmid^(+)80 mg/kg Sch B),with 6 rats in each group.Except the control group,6 groups of rats were sensitized and stimulated with ovalbumin to establish asthma rat model,and were given drug intervention,once a day for four weeks.RT-qPCR was applied to measure the expression of Noxa in lung tissue;differential white blood cell counts in bronchoalveolar lavage fluid(BALF)were performed;ELISA was applied to measure the levels of IL-4,INF-α,IL-13 and IL-5 in rat serum;HE staining was applied to observe the histopathology of lung tissue of rats in each group;expression of Noxa protein and phosphorylation levels of Hsp27 and NF-κB in lung tissue were detected by Western blot.Results:Compared with the Vector group,the expression level of Noxa in the left lung tissue of the Noxa group was obviously increased;compared with the control group,the right lung tissue structure of the rats in the asthma group was obviously damaged,the tracheal tube was obviously narrowed,the interstitium was massively inflammatory infiltration,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the circumference of the basement membrane were obviously increased,and the cells in the BALF were obviously increased,the total number,eosinophils,neutrophils,and lymphocytes were obviously increased,and macrophages were obviously decreased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously increased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tis

关 键 词：哮喘 五味子乙素 Noxa/Hsp27/NF-κB 气道炎症 气道重塑 

分 类 号：R285.5[医药卫生—中药学]