不同剂量1,25-(OH)2D3对哮喘小鼠肺内高迁移率族蛋白B1及IL-17表达的影响

李彦玲; 栾斌; 乔俊英; 张丽敏

doi:10.7499/j.issn.1008-8830.2015.02.017

PDF(2688 KB)

HTML

中国当代儿科杂志 ›› 2015, Vol. 17 ›› Issue (2) : 190-195. DOI: 10.7499/j.issn.1008-8830.2015.02.017

论著·实验研究

不同剂量1,25-(OH)₂D₃对哮喘小鼠肺内高迁移率族蛋白B1及IL-17表达的影响

李彦玲, 栾斌, 乔俊英, 张丽敏

作者信息 +

Effects of different doses of 1,25-(OH)₂D₃ on expression of HMGB1 and IL-17 in the lungs of asthmatic mice

LI Yan-Ling, LUAN Bin, QIAO Jun-Ying, ZHANG Li-Min

Author information +

文章历史 +

摘要

目的观察不同剂量1,25-二羟基维生素D₃ [1,25-(OH)₂D₃]对哮喘小鼠肺内高迁移率族蛋白B1(HMGB1)及IL-17表达的影响.方法将50只BALB/c小鼠随机分为对照组、哮喘组、低剂量组、中剂量组和高剂量组,每组10只.卵清蛋白混合液致敏并雾化吸入建立哮喘小鼠模型,低、中、高剂量组在每次激发前分别按1、4、10 μg/kg给予腹腔注射1,25-(OH)₂D₃混合液,对照组和哮喘组以生理盐水替代.采用苏木精-伊红染色观察小鼠气道结构变化;免疫组化染色观察HMGB1、IL-17蛋白表达的变化,RT-PCR检测HMGB1及IL-17 mRNA水平的表达变化.结果哮喘组气道壁厚度、HMGB1和IL-17的 mRNA及蛋白表达水平均明显高于对照组(P<0.05);低、中剂量组气道壁厚度、HMGB1和IL-17的 mRNA及蛋白表达水平均明显低于哮喘组,且上述指标在中剂量组均明显低于低剂量组(P<0.05);但高剂量组中气道壁厚度、HMGB1和IL-17的 mRNA及蛋白表达水平均高于哮喘组(P<0.05).结论 HMGB1及IL-17可能参与哮喘气道重塑过程;适量1,25-(OH)₂D₃能改善哮喘小鼠气道重塑,大剂量1,25-(OH)₂D₃可加重气道重塑.

Abstract

Objective To study the effects of 1,25-(OH)₂D₃ on airway remodeling and expression of high mobility group box 1 (HMGB1) and IL-17 in asthmatic mice. Methods Fifty female mice were randomly divided into 5 groups: control, asthma, low-dose, middle-dose, and high-dose intervention groups (n=10 each). Asthma was induced by intraperitoneal injections of ovalbumin (OVA) and aerosol inhalation of OVA solution. The low-dose, middle-dose, and high-dose intervention groups were administered with 1,25-(OH)₂D₃ solution at the dosage of 1, 4 and 10 μg/kg respectively by intraperitoneal injections before asthma challenge. The airway structural changes were assessed by hematoxylin and eosin staining. mRNA expression levels of HMGB1 and IL-17 in the lung tissues were evaluated by RT-PCR. The protein levels of HMGB1 and IL-17 in the lung tissues were observed by immunohistochemistry. Results The airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 were higher in the untreated asthma group than in the control group (P<0.05). The airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 were lower in the middle-dose and low-dose intervention groups than in the untreated asthma group, and the middle-dose intervention group demonstrated lower airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 than in the low-dose intervention group (P<0.05). However, the airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 in the high-dose intervention group were higher than in the untreated asthma group (P<0.05). Conclusions HMGB1 and IL-17 may be involved in the airway remodeling process in asthmatic mice. A moderate amount of HMGB1 and IL-17 may be involved in the airway remodeling process in asthmatic mice. A moderate amount of 1,25-(OH)₂D₃ can improve the airway remodeling, but a higher dose of 1,25-(OH)₂D₃ may affect adversely the airway remodeling process.

导出引用

李彦玲, 栾斌, 乔俊英, 张丽敏. 不同剂量1,25-(OH)₂D₃对哮喘小鼠肺内高迁移率族蛋白B1及IL-17表达的影响[J]. 中国当代儿科杂志. 2015, 17(2): 190-195 https://doi.org/10.7499/j.issn.1008-8830.2015.02.017

LI Yan-Ling, LUAN Bin, QIAO Jun-Ying, ZHANG Li-Min. Effects of different doses of 1,25-(OH)₂D₃ on expression of HMGB1 and IL-17 in the lungs of asthmatic mice[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(2): 190-195 https://doi.org/10.7499/j.issn.1008-8830.2015.02.017

参考文献

[1] Braman S. The global burden of asthma[J]. Chest, 2006, 130(1 Suppl): 4S-12S.
[2] Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex,heterogeneous disease[J]. Lancet, 2008, 372(9643): 1107-1119.
[3] 张婷, 夏敏. 高迁移率族蛋白B1信号转导通路的研究进展[J]. 医学综述, 2011, 17(2): 195-198.
[4] 王晨宇, 王星, 王琳, 等. Th17细胞分化调节机制及与自身免疫性疾病关系研究进展[J].细胞与分子免疫学杂志, 2014, 30(6): 660-662.
[5] 王亚哲, 栾斌, 张艳丽, 等. 1,25-(OH)₂D₃对哮喘小鼠肺内TIM-4表达的影响[J]. 中国当代儿科学杂志, 2013, 15(1): 68-70.
[6] Heelings PW, Kasran A, Liu Z, et al. Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma[J]. Am J Respir Cell Mol Biol, 2003, 28(1): 42-50.
[7] Zhang F, Huang G, Hu B, et al. Anti-HMGB1 neutralizing antibody ameliorates neutrophilic airway inflammation by suppressing dendritic cell-mediated Th17 polarization[J]. Mediators Inflamm, 2014, 2014: 257930.
[8] Wang YH, Liu YJ. The IL-17 cytokine family and their role in allergic inflammation[J]. Curr Opin Immunol, 2008, 20(6): 697-702.
[9] Shim EJ, Chun E, Lee HS, et al. The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma[J]. Clin Exp Allergy, 2012, 42(6): 958-965.
[10] He Z, Shotorbani SS, Jiao Z, et al. HMGB1 promotes the differentiation of Th17 via up-regulating TLR2 and IL-23 of CD14+ monocytes from patients with rheumatoid arthritis[J]. Scand J Immunol, 2012, 76(5): 483-490.
[11] 谷惠如, 栾斌, 乔俊英, 等. 1,25-(OH)₂D₃对哮喘小鼠肺内高迁移率族蛋白B1及Toll样受体4表达的影响[J]. 中国当代儿科学杂志, 2014, 16(3): 301-305.
[12] Hewison M. Vitamin D and immune function: an overview[J]. Proc Nutr Soc, 2012, 71(1): 50-61.
[13] Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences[J]. Am J Clin Nutr, 2008, 87(4): 1080S-1086S.
[14] Ryz NR, Patterson SJ, Zhang Y, et al. Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to citrobacter rodentium by syppressing mucosal Th17 responses [J]. Am J Physiol, 2012, 303(12): 1299-1311.
[15] Colin EM, Asmawidjaja PS, van Hamburg JP, et al. 1,25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis[J]. Arthritis Rheum, 2010, 62(1): 132-142.
[16] Giarratana N, Penna G, Amuchastegui S, et al. A vitamin D analog down-regulates proinflammatory chemokine production by pancreatic islets inhibiting T cell recruitment and type 1 diabetes development[J]. J Immunol, 2004, 173(4): 2280-2287.
[17] 宋颖芳, 赖国祥, 柳德灵, 等. 1,25-二羟基维生素D₃抑制慢性哮喘模型小鼠肺组织α-平滑肌肌动蛋白的表达及气道重塑[J]. 实用医学杂志, 2012, 28(21): 3517-3520.
[18] Matheu V, Back O, Mondoc E, et al. Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: Enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease[J]. J Allergy Clin Immunol, 2003, 112(3): 585-592.