天山花楸通过调节Th1/Th2免疫失衡抗哮喘作用及机制研究  

Sorbus tianschanica Rupr.Treats Asthma by Regulating Th1/Th2 Imbalance

作　　者：屯妮萨古丽·艾买提江 马晓丽[1] 常军民[1] 李改茹[1] Tunnisaguli·Aimaitijiang;MA Xiaoli;CHANG Junmin;LI Gairu(College of Pharmacy,Xinjiang Medical University,Urumqi 830017)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830017

出　　处：《中药药理与临床》2024年第4期90-95,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：新疆维吾尔自治区重大科技专项(编号:2022A03007-3)。

摘　　要：目的:探讨天山花楸抗哮喘作用及机制。方法:将SPF级60只雄性SD大鼠随机分为正常对照组、模型对照组、天山花楸1、2、4 g/kg组、地塞米松2 mg/kg组。除正常对照组外,其余组采用卵清蛋白腹腔注射(10%OVA)和雾化(2%OVA)进行造模,造模成功后,各组灌胃给予相应药物,1次/d,连续给药14 d,每天观察大鼠一般状态。采用无创肺功能测试仪检测哮喘大鼠肺功能、收集其血清、BALF、肺脏及脾脏等样本;HE染色观察肺组织病理改变;流式细胞术检测Th1、Th2细胞体积分数;ELISA法检测血清及BALF中的总IgE、OVA-IgE、IFN-γ、IL-4、TNF-α及IL-6含量;Western-blot法检测肺组织中HMGB1、TLR4、MyD88、NF-kBp65、IκBα蛋白表达。结果:与正常对照组比较,模型对照组大鼠出现明显的哮喘症状、气道高反应性明显增强、肺组织出现明显病理改变、脾脏中Th2细胞体积分数明显增加、Th1细胞体积分数明显降低(P<0.05),血清和肺泡灌洗液中总IgE、OVA-IgE、IL-4、TNF-α和IL-6含量明显增加、IFN-γ含量明显降低(P<0.05),肺组织中HMGB1、TLR4、MyD88、NF-κB蛋白表达明显上调,IκBα蛋白表达明显下调(P<0.05);与模型对照组比较,天山花楸1、2、4 g/kg组、地塞米松2 mg/kg组大鼠哮喘症状明显减轻、气道高反应性明显降低(P<0.05)、肺组织病变情况有所改善,脾脏Th2细胞体积分数明显降低、Th1细胞体积分数明显增加(P<0.05),Th1/Th2趋向平衡,血清和肺泡灌洗液中总IgE、OVA-IgE、IL-4、TNF-α和IL-6含量明显降低,IFN-γ含量明显增高(P<0.05),肺组织中HMGB1、TLR4、MyD88、NF-κB蛋白表达明显下调,IκBα蛋白表达量明显上调(P<0.05)。结论:天山花楸水提物具有抗哮喘药理活性,其抗哮喘作用机制可能是通过调节Th1/Th2免疫失衡,抑制HMGB1/TLR4/NF-κB信号通路激活实现的。Objective:To investigate the anti-asthmatic effect and mechanism of Sorbus tianschanica Rupr.Methods:Sixty male SD rats of SPF grade were randomized into normal control,model,Sorbus tianschanica(1,2,and 4 g/kg),and dexamethasone(2 mg/kg)groups.The rats in other groups except the normal control group were treated with ovalbumin(OVA)by intrabitoneal injection(10%OVA)and atomization(2%OVA)for the modeling of asthma.After successfully modeling,rats in each group were treated with corresponding drugs once a day for 14 consecutive days,and the general state of the rats was observed daily.A noninvasive animal pulmonary function tester was used to measure the lung function,and the serum,bronchoalveolar lavage fluid(BALF),lung,and spleen samples were collected.The pathological changes of the lung tissue were observed by hematoxylin-eosin staining.The levels of Th1 and Th2 cells were determined by flow cytometry.Enzyme-linked immunosorbent assay was employed to determine the levels of total IgE,OVA-IgE,interferon(IFN)-γ,interleukin(IL)-4,tumor necrosis factor(TNF)-α,and IL-6 in the serum and BALF.Western blotting was employed to determine the protein levels of high mobility group box 1(HMGB1),Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor-kappa B(NF-κB)p65,and inhibitor proteinαof NF-κB(IκBα)in the lung tissue.Results:Compared with the normal control group,the model control group showed obvious asthma symptoms,increased airway hyperresponsiveness(P<0.05),obvious lesions in the lung tissue,increased Th2 cells and decreased Th1 cells in the spleen(P<0.05),and elevated levels of total IgE,OVA-IgE,IL-4,TNF-α,and IL-6 and lowered IFN-γlevel in the serum and BALF(P<0.05).Furthermore,the model group showed up-regulated protein levels of HMGB1,TLR4,MyD88,and NF-κB and down-regulated protein level of IκBαin the lung tissue(P<0.05).Compared with the model group,S.tianschanica(1,2,and 4 g/kg)and dexamethasone(2 mg/kg)alleviated the asthma symptoms and airway hyperreactivity(P<0.05),miti

关 键 词：天山花楸 哮喘 气道高反应性 TH细胞 细胞因子 TOLL样受体4 髓样分化因子88 高迁移率蛋白1 

分 类 号：R285[医药卫生—中药学]