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橘红桔梗植物饮品对小鼠急性肺损伤和支气管哮喘的预防作用研究OA北大核心CSTPCD

Preventive effect of Tangerine-Platycodon Complex on acute lung injury and bronchial asthma in mice

中文摘要英文摘要

目的:观察橘红桔梗植物饮品(TPC)对脂多糖诱导的小鼠急性肺损伤(ALI)和卵清蛋白诱导的小鼠支气管哮喘的影响,并分析其作用机制.方法:(1)将48只雄性C57BL/6小鼠随机分成空白对照组、ALI组及低、中、高剂量(0.8、1.6和3.2 mL/d)TPC组,灌胃给药,每日1次,持续1周及地塞米松阳性对照组.采用脂多糖气管内滴注建立小鼠ALI模型.采用HE染色法观察肺组织病理变化;流式细胞分析仪检测支气管肺泡灌洗液(BALF)中性粒细胞比例;ELISA检测BALF中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6和IL-10含量;同时检测肺组织匀浆中的髓过氧化物酶(MPO)活性及肺组织中I-κBα和NF-κB的蛋白含量.(2)将48只雌性C57BL/6小鼠随机分成空白对照组、支气管哮喘组及低、中、高剂量(0.8、1.6和3.2 mL/d)TPC组,灌胃给药,每日1次,持续1周及地塞米松组.采用卵清蛋白腹腔注射致敏和鼻内刺激建立支气管哮喘小鼠模型.采用HE染色和甲苯胺蓝染色法观察肺组织病理变化;ELISA检测小鼠血清中IgE、IL-5和IL-13含量.结果:与空白对照组相比,ALI组小鼠肺组织病理学显示明显炎症细胞浸润;BALF中的中性粒细胞比例、MPO活性及TNF-α、IL-1β和IL-6含量显著升高(P<0.05),IL-10含量降低(P<0.05);Western blot结果显示肺组织中I-κBα 蛋白含量降低,磷酸化NF-κB的蛋白含量升高(P<0.05).与ALI组比较,高剂量TPC组和地塞米松组小鼠肺组织病理炎症明显减轻;BALF中的中性粒细胞比例、髓过氧化物酶活性及TNF-α、IL-1β和IL-6含量明显降低(P<0.05),IL-10含量升高(P<0.05);肺组织中I-κBα 蛋白含量升高,磷酸化NF-κB的蛋白含量降低(P<0.05).与空白对照组比较,支气管哮喘组小鼠肺组织病理有明显的炎症细胞及肥大细胞浸润;小鼠血清中的IgE和IL-13含量升高(P<0.05).与支气管哮喘组相比,高剂量TPC组和地塞米松组小鼠肺组织病理炎症细胞及肥大细胞减少;小鼠血清中的IgE含量下降(P<0.05).地塞米松组小鼠IL-13含量下降(P<0.05).结论:TPC能在一定程度上预防脂多糖诱导的小鼠ALI,减轻支气管哮喘模型小鼠的过敏反应,其机制与抑制炎症反应、减少肥大细胞浸润和IgE生成有关.

AIM:This study aims to analyze the effects of Tangerine Platycodon Complex(TPC)on lipopoly-saccharide-induced acute lung injury and ovalbumin-induced bronchial asthma in mice,as well as its mechanism of ac-tion.METHODS:(1)Forty-eight male C57BL/6 mice were randomly divided into normal,acute lung injury,low,medi-um,and high dose(0.8,1.6 and 3.2 mL/d)of TPC groups,which were administered by gavage once a day for one week.Dexamethasone was used as a positive control.The acute lung injury mouse model was established through intratra-cheal administration of lipopolysaccharide.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)staining.The number of neutrophils in alveolar lavage fluid was determined using flow cytometry.ELISA was used to determine the concentrations of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),IL-6 and IL-10,and to detect myeloperoxidase(MPO)activity in lung tissue homogenate and the protein content of I-κBα and NF-κB in lung tis-sue.(2)Forty-eight female C57BL/6 mice were randomly divided into the following groups:normal,bronchial asthma,low-,medium-,and high-dose groups(0.8,1.6 and 3.2 mL/d)of TPC,and the dexamethasone group.The mice were orally administered once a day for one week.A mouse model of bronchial asthma was established by intraperitoneal injec-tion of ovalbumin for sensitization and nasal stimulation.HE and toluidine blue staining were used to observe pathological changes in lung tissue,and the concentrations of IgE,IL-5,and IL-13 in mouse serum were determined using ELISA.RESULTS:Compared to the control group,mice in the acute lung injury group exhibited significant inflammatory cell in-filtration in the lung tissue.In bronchoalveolar lavage fluid(BALF),the percentage of neutrophils and MPO activity,and TNF-α,IL-1β,and IL-6 levels increased significantly(P<0.05),while IL-10 concentration decreased(P<0.05).West-ern blot revealed that the protein content of I-κBα decreased while NF-κB phosphorylation increased(P<0.05).Inflam-mation of lung tissue in the high-dose TPC and dexamethasone groups was significantly reduced.The percentage of neutro-phils,MPO activity in BALF,and the levels of TNF-α,IL-1β,and IL-6 significantly decreased(P<0.05),whereas IL-10 levels increased(P<0.05).The protein content of I-κBα increased in the lung tissue,whereas the levels of NF-κB phosphorylation were reduced(P<0.05).Compared to the normal group,mice in the bronchial asthma group exhibited significant inflammatory cell and mast cell infiltration.IgE and IL-13 levels in mouse serum increased(P<0.05).The pathological inflammatory cells and mast cells in the lung tissue of mice in the high-dose TPC and dexamethasone groups decreased compared to those in the bronchial asthma group,while mouse serum IgE levels decreased(P<0.05).More-over,IL-13 levels in dexamethasone-treated mice decreased(P<0.05).CONCLUSION:The acute lung injury induced by lipopolysaccharide in mice can be partially prevented by TPC.Additionally,it improved allergic reactions in mice with bronchial asthma by inhibiting the inflammatory response and reducing mast cell infiltration and IgE production.

刘岩;唐冬梅;段蕊;肖素军;林润;黄锦容;赵明

南方医科大学基础医学院病理生理学系,广东省休克与微循环研究重点实验室,广东 广州 510515南华大学衡阳医学院附属南华医院心血管内科,湖南 衡阳 421001南方医科大学基础医学院病理生理学系,广东省休克与微循环研究重点实验室,广东 广州 510515||南华大学衡阳医学院附属南华医院心血管内科,湖南 衡阳 421001

临床医学

橘红桔梗植物饮品急性肺损伤支气管哮喘炎症过敏反应

Tangerine-Platycodon Complexacute lung injurybronchial asthmainflammationallergy

《中国病理生理杂志》 2024 (004)

653-661 / 9

国家自然科学基金资助项目(No.81974045)

10.3969/j.issn.1000-4718.2024.04.010

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