摘要
目的探究维生素D_(3)(VitD_(3))在小鼠支气管哮喘气道炎症和氧化应激反应中的作用和相关分子机制。方法将28只雌性C57BL/6小鼠随机分为对照组(Ctrl)和模型组。模型组小鼠采用卵清蛋白(OVA)致敏法建立哮喘模型后,将其分为哮喘(Asthma)组、VitD_(3)处理(Asthma+VitD_(3))组和叉头盒O1(FOXO1)抑制剂AS1842856处理(Asthma+AS)组。测定各组小鼠肺阻力(LR)变化。采用ELISA法检测肺泡灌洗液(BALF)中炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和IL-18的含量。Western blot检测肺组织中FOXO1和NOD样受体热蛋白结构域相关蛋白3(NLRP3)、半胱氨酸天冬氨酸酶-1(Caspase-1)和凋亡斑点蛋白(ASC)的表达水平。结果与Ctrl组相比,Asthma组小鼠的LR升高(P<0.01)。与Asthma组相比,Asthma+VitD_(3)组和Asthma+AS组小鼠的LR降低(P<0.05),Asthma+VitD_(3)组与Asthma+AS组小鼠的LR变化差异无统计学意义。与Ctrl组相比,Asthma组、Asthma+VitD_(3)组和Asthma+AS组小鼠BALF中TNF-α、IL-1β与IL-18含量均增加(P<0.01),肺组织中NLRP3、Caspase-1和ASC蛋白表达水平均升高(P<0.01);与Asthma组相比,Asthma+VitD_(3)组和Asthma+AS组小鼠BALF中上述炎症因子含量均减少(P<0.05),肺组织中NLRP3、FOXO1、Caspase-1和ASC蛋白表达均降低(P<0.05);与Asthma+VitD_(3)组相比,Asthma+AS组中除FOXO1蛋白表达水平升高外(P<0.05),上述其他检测指标差异均无统计学意义。结论VitD_(3)可减轻OVA诱导的小鼠哮喘症状,改善气道炎症程度和降低氧化应激水平,且其机制可能与FOXO1/NLRP3轴的下调有关。
Objective To investigate the role and related molecular mechanisms of vitamin D 3(VitD 3)in airway inflammation and oxidative stress response in bronchial asthma mice.Methods Twenty-eight female C57BL/6 mice were randomly divided into a control group(Ctrl)and a model group.The model group mice were sensitized using ovalbumin(OVA)to establish an asthma model,and were further divided into an asthma(Asthma)group,VitD 3 treatment(Asthma+VitD 3)group,and Forkhead Box O1(FOXO1)inhibitor AS1842856 treatment(Asthma+AS)group.Lung resistance(LR)changes were measured in each group of mice.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,and IL-18 in bronchoalveolar lavage fluid(BALF).Western blot was used to determine the expression levels of FOXO1,NOD-like receptor pyrin domain containing 3(NLRP3),Caspase-1,and apoptosis-associated speck-like protein(ASC)in lung tissue.Results Compared to the Ctrl group mice,LR increased in the Asthma group mice(P<0.01).Compared to the Asthma group,LR decreased in the Asthma+VitD 3 and Asthma+AS group mice(P<0.05),with no significant difference in LR change between Asthma+VitD 3 and Asthma+AS group mice.Compared to the Ctrl group,TNF-α,IL-1β,and IL-18 levels in BALF,as well as NLRP3,Caspase-1,and ASC protein expression levels in lung tissue,increased in the Asthma,Asthma+VitD 3,and Asthma+AS group mice(P<0.05).Compared to the Asthma group,the Asthma+VitD 3 and Asthma+AS group mice showed decreased levels of the mentioned inflammatory factors in BALF and reduced protein expression of NLRP3,FOXO1,Caspase-1,and ASC in lung tissue(P<0.05).Compared to the Asthma+VitD 3 group,the Asthma+AS group showed increased FOXO1 protein expression(P<0.05),with no statistically significant differences in the other measured indicators.Conclusion VitD 3 can alleviate asthma symptoms induced by OVA in mice,improve the degree of airway inflammation,and reduce oxidative stress levels.The mechanism may be related to the downregulati
作者
贾斌
梁思敏
Jia Bin;Liang Simin(Dept of Respiratory,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054)
出处
《安徽医科大学学报》
CAS
北大核心
2024年第1期58-63,共6页
Acta Universitatis Medicinalis Anhui
基金
新疆维吾尔自治区自然科学基金(编号:2019D01C294)。
