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山东大学学报 (医学版) ›› 2017, Vol. 55 ›› Issue (12): 18-23.doi: 10.6040/j.issn.1671-7554.0.2017.658

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肌球蛋白轻链激酶对哮喘小鼠气道炎症及肺功能的影响

宫晓丹1,2,赵方正2,3,曹可1,2,邓鹏辉2,张才擎2   

  1. 1. 山东大学临床医学院, 山东 济南 250012;2. 山东大学附属千佛山医院呼吸内科, 山东 济南 250014;3. 山东中医药大学第二附属医院, 山东 济南 250001
  • 出版日期:2017-12-20 发布日期:2022-09-27
  • 通讯作者: 张才擎. E-mail:freezcq66@163.com

Effect of myosin light chain kinase on airway inflammation and lung function in asthma model mice

GONG Xiaodan1,2, ZHAO Fangzheng2,3, CAO Ke1,2, DENG Penghui2, ZHANG Caiqing2   

  1. 1. Medical College of Shandong University, Jinan 250012, Shandong, China;
    2. Respiratory Physicians of Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
    3. The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, Shandong, China
  • Online:2017-12-20 Published:2022-09-27

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摘要： 目的 研究肌球蛋白轻链激酶(MLCK)在哮喘小鼠气道中的表达及其对哮喘气道炎症和肺功能的影响。 方法 将20只雌性BALB/c小鼠随机分为对照组(n=10)及哮喘组(n=10),利用鸡卵白蛋白(OVA)建立小鼠哮喘模型。光学显微镜下计数血清中白细胞及嗜酸性粒细胞总数;ELISA方法检测肺泡灌洗液中炎性介质IL-4、IFN-γ水平; Western blotting法检测小鼠肺组织MLCK的表达;免疫实时荧光定量(qPCR)检测MLCK在基因水平的表达。 结果 肺功能检测示哮喘组小鼠最大呼气流量峰值(PEF)、第0.4秒用力呼气容积占用力肺活量比值(FEV0.4/FVC)均低于对照组(P均<0.001);哮喘组小鼠白细胞及嗜酸性粒细胞计数均高于对照组(P均<0.001);ELISA结果示哮喘组小鼠BALF中炎性介质IL-4浓度较对照组明显升高(P<0.001),而IFN-γ浓度较对照组降低(P<0.001);哮喘组小鼠肺组织MLCK表达量明显升高(P=0.006);与对照组相比,哮喘组MLCK在基因水平上的表达升高(P<0.001)。 结论 MLCK可能参与哮喘气道炎症反应并影响肺功能。

关键词: 哮喘, 肌球蛋白轻链激酶, 肺功能, IL-4, INF-γ

Abstract: Objective To study the effect of myosin light chain kinase(MLCK)on airway inflammation and pulmonary function through the determination of its expression in asthmatic mice airway. Methods Twenty female BALB/c mice were randomly divided into normal control group(n=10)and asthma group(n=10). Mice model of asthma was established by using chicken ovalbumin(OVA). The counts of leukocytes and eosinophilic granulocytes were observed with optical microscope. The expressions of the inflammatory mediators as IL-4 and IFN-γ in bronchoalveolar lavage fluid(BALF)were detected by ELISA kit. The expression of MLCK in the lung tissue of asthmatic mice was detected by Western blotting. The expression of MLCK in the gene level was detected by qPCR. Results The lung function test showed that peak expiratory flow(PEF), the ratio of forced expiratory volume in 0.4 second to forced vital capacity(FEV0.4/FVC)in asthma group was lower than those in normal control group(P<0.001). The counts of leukocytes and eosinophilic granulocytes in asthma group were higher than those in normal control group(P<0.001). The IL-4 level in the BALF in asthma group was higher than that in normal control group(P<0.001), while the IFN-γ level 山 东 大 学 学 报 (医 学 版)55卷12期 -宫晓丹,等.肌球蛋白轻链激酶对哮喘小鼠气道炎症及肺功能的影响 \=-was lower than that in nornal control group(P<0.001). The expression of MLCK in the lung tissue of asthma group was significantly increased(P=0.006). The expression of MLCK in the gene level of asthma group was higher compared with the normal control group(P<0.001). Conclusion MLCK may be involved in the airway inflammation response and influence the lung function.

Key words: Asthma, Myosin light chain kinase, Lung function, IL-4, IFN-γ

中图分类号: 

  • R562.2+5
[1] Wang Y, Bai C, Li K, et al. Role of airway epithelial cells in development of asthma and allergic rhinitis[J]. Respir Med, 2008, 102(7): 949-955.
[2] Deckers J, Branco Madeira F, Hammad H. Innate immune cells in asthma[J]. Trends Immunol, 2013, 34(11): 540-547.
[3] Luzina IG, Lockatell V, Lavania S, et al. Natural production and functional effects of alternatively spliced interleukin-4 protein in asthma[J]. Cytokine, 2012, 58(1): 20-26.
[4] Liu Y, Zhuo A, Liu W, et al. The-33C/T polymorphism in the interleukin 4 gene is associated with asthma risk: a meta-analysis[J]. J Investig Allergol Clin Immunol, 2014, 24(2): 114-121.
[5] 于华凤,王广新,韩玉玲,等. 儿童支气管哮喘血清IL-4、IL-10和IFN-γ浓度的测定及其临床意义[J]. 中华哮喘杂志(电子版), 2010, 4(5): 320-323. YU Huafeng, WANG Guangxin, HAN Yuling, et al. Levels of serum IL-4, IL-10, IFN-γ in children with bronchial asthma and their clinical significance[J]. Chin J Asthma(Electronic Edition), 2010, 4(5): 320-323.
[6] Ma X, Cheng Z, Kong H, et al. Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjecrs[J]. Am J of Physiol Lung Cell Mol Physiol, 2002, 283(6):1181-1189.
[7] Bousquet J, Jeffery PK, Busse WW, et al. Asthma. From bronchoconstriction to airways inflammation and remodeling[J]. Am J Respir Crit Care Med, 2000, 161(5): 1720-1745.
[8] Lambert RK, Wiggs BR, Kuwano K, et al. Functional significance of increased airway smooth muscle in asthma and COPD[J]. J Appl Physiol, 1993, 74(6): 2771-2781.
[9] Chen C, Kudo M, Rutaganira F, et al. Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing[J]. J Clin Invest, 2012, 122(8): 2916-2927.
[10] Kudo M, Melton AC, Chen C, et al. IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction[J]. Nat Med, 2012, 18(4): 547-554.
[11] 赵彩霞. 支气管哮喘发病机制的研究进展[J]. 医学理论与实践, 2016, 29(7): 870-872.
[12] 李文娟,高超. 支气管哮喘的变态反应机制[J]. 临床医药实践, 2013, 22(1): 44-46.
[13] Romagnani S. Immunologic influences on allergy and the TH1/TH2 balance[J]. J Allergy and Clin Immunol, 2004, 113(3): 395-400.
[14] 曲书强,张磊,吴静,等.干扰素-γ对小鼠哮喘模型治疗的研究[J]. 现代生物医学进展, 2009, 9(2): 230-231. QU Shuqiang, ZHANG Lei, WU Jing, et al. A study on IFN-γ in treatment of asthma mice[J]. Progress in Modern Biomedicine, 2009, 9(2): 230-231.
[15] Packard KA. Effects of histamine on Th1/Th2 cytokine balance[J]. Int Immunopharmacol, 2003, 3(7): 909-920.
[16] Wu C, Yang G, Bermúdez-Humarán LG, et al. Immunomodulatory effects of IL-12 secreted by Lactococcus lactis on Th1/Th2 balance in ovalbumin(OVA)-induced asthma model mice[J]. Int Immunopharmacol, 2006, 6(4): 610-615.
[17] Shen H, Xia L, Lu J, et al. Interleukin-4 in rheumatoid arthritis patients with interstitial lung disease: a pilot study[J]. Indian J Med Res, 2013, 138(6): 919-921.
[18] Luzina IG, Lockatell V, Todd NW, et al. Alternatively spliced variants of interleukin-4 promote inflammation differentially[J]. J Leukoc Biol, 2011, 89(5): 763-770.
[19] Zhang HF, Li TB, Liu B, et al. Inhibition of myosin light chain kinase reduces NADPH oxidase-mediated oxidative injury in rat brain following cerebral ischemia/reperfusion[J]. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(9): 953-963.
[20] 易在凤,范恒,杨佳.肌球蛋白轻链激酶在炎症性肠病中的作用[J]. 世界华人消化杂志, 2014, 22(35): 5467-5472. YI Zaifeng, FAN Heng, YANG Jia. Role of myosin light chain kinase in inflammatory bowel disease[J]. World Chinese Journal of Digestology, 2014, 22(35): 5467-5472.
[21] Schmidt D, Rabe KF. Immune mechanisms of smooth muscle hyperreactivity in asthma[J]. J Allergy Clin Immunol, 2000, 105(4): 673-682.
[22] 孙艳宏. 气道平滑肌细胞中GLP-1受体的表达对细胞增殖及炎症因子的调节机制研究[D]. 广州:南方医科大学, 2016.
[23] 张贞贞,莫碧文.气道平滑肌细胞作为免疫调节细胞与支气管哮喘炎症的关系[J]. 中华哮喘杂志(电子版), 2012, 6(1): 39-43. ZHANG Zhenzhen, MO Biwen. Airway smooth muscle cell as an immunomodulatory cell in inflammatory reaction in bronchial asthma[J]. Chin J Asthma(Electronic Edition), 2012, 6(1): 39-43.
[24] Howarth PH, Knox AJ, Amrani Y, et al. Synthetic responses in airway smooth muscle.[J]. J Allergy Clin Immunol, 2004, 114(114): 32-50.
[25] Damera G, Tliba O, Panettieri RA, et al. Airway smooth muscle as an immunomodulatory cell[J]. Pulm Pharmacol Ther, 2009, 22(5): 353-359.
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