1α,25-二羟基维生素D3对哮喘小鼠SIRT1、GATA-3表达及气道炎症水平的影响
R562.25; 目的 探究1α,25-二羟基维生素D3对哮喘小鼠气道炎症变化的影响及可能机制.方法 将24只SPF级BALB/c小鼠随机分为对照组、哮喘组、哮喘+1α,25-二羟基维生素D3(哮喘+VD3)组,每组8只.哮喘组和哮喘+VD3组小鼠于第1、8、15天给予卵清蛋白(OVA)混悬液0.2 ml致敏,对照组给予生理盐水0.2 ml;哮喘组和哮喘+VD3组于第22～28天使用1%OVA雾化吸入激发,对照组给予等量生理盐水雾化吸入,每次雾化30 min,1次/d,连续激发7 d;哮喘+VD3组每次雾化前30 min给予1α,25-二羟基维生素D3注射液(4 μg/kg),对照组和哮喘组给...
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| Published in | 解放军医学杂志 Vol. 49; no. 6; pp. 686 - 693 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
兰州大学第一临床医学院,甘肃兰州 730000%兰州大学第一医院呼吸与危重症医学科,甘肃兰州 730000
28.06.2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0577-7402 |
| DOI | 10.11855/j.issn.0577-7402.0520.2023.1204 |
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| Abstract | R562.25; 目的 探究1α,25-二羟基维生素D3对哮喘小鼠气道炎症变化的影响及可能机制.方法 将24只SPF级BALB/c小鼠随机分为对照组、哮喘组、哮喘+1α,25-二羟基维生素D3(哮喘+VD3)组,每组8只.哮喘组和哮喘+VD3组小鼠于第1、8、15天给予卵清蛋白(OVA)混悬液0.2 ml致敏,对照组给予生理盐水0.2 ml;哮喘组和哮喘+VD3组于第22～28天使用1%OVA雾化吸入激发,对照组给予等量生理盐水雾化吸入,每次雾化30 min,1次/d,连续激发7 d;哮喘+VD3组每次雾化前30 min给予1α,25-二羟基维生素D3注射液(4 μg/kg),对照组和哮喘组给予等量生理盐水.最后一次激发后麻醉处理采集小鼠血清、支气管肺泡灌洗液(BALF)和肺组织标本.采用HE染色和PAS染色观察肺组织病理学改变及气道黏液水平的变化;ELISA法检测血清IgE及BALF中炎性因子白细胞介素(IL)-4、IL-5、IL-13水平;免疫组化、Western blotting检测小鼠肺组织中沉默信息调节因子1(SIRT1)和GATA结合蛋白-3(GATA-3)的表达情况.采用Pearson直线相关分析肺组织SIRT1、GATA-3表达水平(SIRT1、GATA-3的平均OD值)与小鼠血清IgE及BALF中IL-4、IL-5、IL-13浓度的相关性.结果 与对照组比较,哮喘组小鼠肺组织气管及伴行血管周围炎性细胞浸润明显增多,其中以嗜酸性粒细胞为主,支气管管腔狭窄,气道黏膜上皮增生,气管内黏液分泌增多;哮喘+VD3组小鼠上述改变较哮喘组减轻.与对照组比较,哮喘组小鼠血清IgE和BALF中IL-4、IL-5、IL-13等炎性因子水平及肺组织中GATA-3表达均增高(P<0.05),肺组织中SIRT1表达降低(P<0.05);与哮喘组比较,哮喘+VD3组小鼠血清IgE和BALF中IL-4、IL-5、IL-13水平及肺组织GATA-3表达均降低(P<0.05),肺组织SIRT1表达增高(P<0.05).相关性分析结果显示,小鼠肺组织SIRT1表达水平与GATA-3表达量、血清IgG及BALF中IL-4、IL-5、IL-13水平均呈负相关(P<0.05);小鼠肺组织GATA-3表达水平与血清IgG及BALF中IL-4、IL-5、IL-13水平均呈正相关(P<0.05).结论 1α,25-二羟基维生素D3可缓解哮喘小 |
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| AbstractList | R562.25; 目的 探究1α,25-二羟基维生素D3对哮喘小鼠气道炎症变化的影响及可能机制.方法 将24只SPF级BALB/c小鼠随机分为对照组、哮喘组、哮喘+1α,25-二羟基维生素D3(哮喘+VD3)组,每组8只.哮喘组和哮喘+VD3组小鼠于第1、8、15天给予卵清蛋白(OVA)混悬液0.2 ml致敏,对照组给予生理盐水0.2 ml;哮喘组和哮喘+VD3组于第22～28天使用1%OVA雾化吸入激发,对照组给予等量生理盐水雾化吸入,每次雾化30 min,1次/d,连续激发7 d;哮喘+VD3组每次雾化前30 min给予1α,25-二羟基维生素D3注射液(4 μg/kg),对照组和哮喘组给予等量生理盐水.最后一次激发后麻醉处理采集小鼠血清、支气管肺泡灌洗液(BALF)和肺组织标本.采用HE染色和PAS染色观察肺组织病理学改变及气道黏液水平的变化;ELISA法检测血清IgE及BALF中炎性因子白细胞介素(IL)-4、IL-5、IL-13水平;免疫组化、Western blotting检测小鼠肺组织中沉默信息调节因子1(SIRT1)和GATA结合蛋白-3(GATA-3)的表达情况.采用Pearson直线相关分析肺组织SIRT1、GATA-3表达水平(SIRT1、GATA-3的平均OD值)与小鼠血清IgE及BALF中IL-4、IL-5、IL-13浓度的相关性.结果 与对照组比较,哮喘组小鼠肺组织气管及伴行血管周围炎性细胞浸润明显增多,其中以嗜酸性粒细胞为主,支气管管腔狭窄,气道黏膜上皮增生,气管内黏液分泌增多;哮喘+VD3组小鼠上述改变较哮喘组减轻.与对照组比较,哮喘组小鼠血清IgE和BALF中IL-4、IL-5、IL-13等炎性因子水平及肺组织中GATA-3表达均增高(P<0.05),肺组织中SIRT1表达降低(P<0.05);与哮喘组比较,哮喘+VD3组小鼠血清IgE和BALF中IL-4、IL-5、IL-13水平及肺组织GATA-3表达均降低(P<0.05),肺组织SIRT1表达增高(P<0.05).相关性分析结果显示,小鼠肺组织SIRT1表达水平与GATA-3表达量、血清IgG及BALF中IL-4、IL-5、IL-13水平均呈负相关(P<0.05);小鼠肺组织GATA-3表达水平与血清IgG及BALF中IL-4、IL-5、IL-13水平均呈正相关(P<0.05).结论 1α,25-二羟基维生素D3可缓解哮喘小 |
| Abstract_FL | Objective To explore the effects of 1α,25-dihydroxyvitamin D3 on airway inflammation in asthmatic mice and the potential mechanisms.Methods Twenty-four female BALB/c mice in SPF grade were randomly divided into three groups(n=8):control group,asthma group,and asthma+VD3 group.On the 1st,8th,and 15th day,asthma group and asthma+VD3 group were given 0.2 ml ovalbumin(OVA)suspension for sensitization,while control group received 0.2 ml normal saline.On the 22-28th day,asthma group and asthma+VD3 group were challenged with 1%OVA atomization inhalation,while control group received an equal amount of normal saline atomization,for 30 minutes each time,once a day,for a continuous 7 days.Asthma+VD3 group was given intraperitoneal injection of 1α,25-dihydroxyvitamin D3 injection(4 μg/kg)30 minutes before each atomization,while control group and asthma group were given an equal dose of normal saline.After the last challenge,all mice were anesthetized,and serum,bronchoalveolar lavage fluid(BALF)and lung tissue samples were collected.HE staining and Periodic Acid Schiff(PAS)staining were used to observe the pathological changes in lung tissue and changes in airway mucus levels.ELISA was employed to detect serum IgE and inflammatory cytokines IL-4,IL-5 and IL-13 in BALF.Immunohistochemical technique and Western blotting were used to detect the expressions of SIRT1 and GATA-3 in mouse lung tissue.Results Compared with control group,asthma group had a significant increase in inflammatory cell infiltration around lung tissue,bronchia and accompanying perivascular,mainly characterized by eosinophils.Bronchial lumen stenosis,airway mucosal epithelial hyperplasia,and increased tracheal mucus secretion were also observed.The above changes in asthma+VD3 group were reduced compared with asthma group.Compared with control group,serum levels of IgE,and IL-4,IL-5,IL-13 inflammatory factors in BALF and GATA-3 in lung tissue were increased in asthma group(P<0.05),and SIRT1 level in lung tissue was significant decreased(P<0.05).Compared with asthma group,IgE level in serum,inflammatory factors of IL-4,IL-5 and IL-13 in BALF,and GATA-3 in lung tissue in asthma+VD3 group were decreased(P<0.05),and SIRT1 level in lung tissue was increased(P<0.05).Correlation analysis showed that the expression level of lung tissue SIRT1 was negatively correlated with the expression of GATA-3,serum IgG,and the levels of IL-4,IL-5,and IL-13 in BALF(P<0.05);the expression level of lung tissue GATA-3 was positively correlated with serum IgG and the levels of IL-4,IL-5,and IL-13 in BALF(P<0.05).Conclusion 1α,25-dihydroxyvitamin D3 can alleviate airway inflammation in asthmatic mice,possibly by upregulating the expression of SIRT1 in lung tissue and inhibiting the expression of GATA-3,thereby inhibiting inflammatory factors(IL-4,IL-5,IL-13). |
| Author | 刘维英 开锦军 王歆 梁雪杰 武晨 |
| AuthorAffiliation | 兰州大学第一临床医学院,甘肃兰州 730000%兰州大学第一医院呼吸与危重症医学科,甘肃兰州 730000 |
| AuthorAffiliation_xml | – name: 兰州大学第一临床医学院,甘肃兰州 730000%兰州大学第一医院呼吸与危重症医学科,甘肃兰州 730000 |
| Author_FL | Wu Chen Kai Jin-Jun Liang Xue-Jie Wang Xin Liu Wei-Ying |
| Author_FL_xml | – sequence: 1 fullname: Wang Xin – sequence: 2 fullname: Liu Wei-Ying – sequence: 3 fullname: Wu Chen – sequence: 4 fullname: Liang Xue-Jie – sequence: 5 fullname: Kai Jin-Jun |
| Author_xml | – sequence: 1 fullname: 王歆 – sequence: 2 fullname: 刘维英 – sequence: 3 fullname: 武晨 – sequence: 4 fullname: 梁雪杰 – sequence: 5 fullname: 开锦军 |
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| DocumentTitle_FL | Effects of 1α,25-dihydroxyvitamin D3 on expression of SIRT1,GATA-3 and airway inflammation in asthmatic mice |
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| Keywords | 沉默信息调节因子1 1α,25-dihydroxyvitamin D3 airway inflammation 1α,25-二羟基维生素D3 气道炎症 GATA结合蛋白-3 bronchial asthma SIRT1 支气管哮喘 GATA-3 |
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| Publisher | 兰州大学第一临床医学院,甘肃兰州 730000%兰州大学第一医院呼吸与危重症医学科,甘肃兰州 730000 |
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| Snippet | R562.25; 目的 探究1α,25-二羟基维生素D3对哮喘小鼠气道炎症变化的影响及可能机制.方法 将24只SPF级BALB/c小鼠随机分为对照组、哮喘组、哮喘+1α,25-二羟基维生素D3(哮喘+VD3)组,每组8只.哮喘组和哮喘+VD3组小鼠于第1、8、15天给予卵清蛋白(OVA)混悬液0.2... |
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| Title | 1α,25-二羟基维生素D3对哮喘小鼠SIRT1、GATA-3表达及气道炎症水平的影响 |
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