辛伐他汀对豚鼠哮喘模型血清IL-4及TGF-β1水平的影响
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摘要
目的通过辛伐他汀对豚鼠哮喘模型血清中IL-4、TGF-β1水平的影响,为辛伐他汀医治哮喘提供实验依据。方法 50只健康豚鼠被随机分为5组:哮喘模型组、S1:20mg/kg辛伐他汀干预组、S2:40 mg/kg辛伐他汀干预组、S3:60 mg/kg辛伐他汀干预组、对照组;每组10只。采用卵蛋白致敏和反复激发制备豚鼠哮喘模型。血清中IL-4、TGF-β1的水平用酶联免疫吸附法(ELISA)检测。结果哮喘模型组、S1组、S2组及S3组IL-4、TGF-β1水平均高于对照组(P<0.01)。其中,哮喘模型组高于辛伐他汀干预组(P <0.05);S1、S3组高于S2组(P <0.05)。结论辛伐他汀可通过降低IL-4水平减轻气道炎症;辛伐他汀可通过降低TGF-β1水平以发挥抑制气道重塑的作用。
Objective To study the impact of simvastatin on serum IL-4,TGF-β1 in the asthma models guinea pigs, to provide the experimental basis for simvastatin treatment of bronchial asthma. Methods Fifty male guinea pigs were randomly divided into five groups: asthmatic model group, S1 group(20 mg/kg simvastatin treat group), S2 group(40 mg/kg simvastatin treat group) and S3 group(60 mg/kg simvastatin treat group) and control group, 10 guinea pigs in each group. The asthmatic models were established by ovalbumin(OVA) sensitization and repeated stimulation. Serum level of IL-4 and TGF-β1 were detected by enzyme-linked immunosorbent assay(ELISA). Results Compared with the control group, the level of IL-4, TGF-β1 in the asthma model group,S1 group,S2 group and S3 group were significantly higher(P < 0.01). The level of IL-4, TGF-β1 in asthma group was higher than simvastatin treat group(P < 0.05). The level of IL-4, TGF-β1 in S1 and S3 group was higher than S2 group(P < 0.05). Conclusion Simvastatin can reduce airway inflammation by lowering the level of IL-4. Simvastatin can inhibit asthma airway remodeling by reducing the level of TGF-β1.
Objective To study the impact of simvastatin on serum IL-4,TGF-β1 in the asthma models guinea pigs, to provide the experimental basis for simvastatin treatment of bronchial asthma. Methods Fifty male guinea pigs were randomly divided into five groups: asthmatic model group, S1 group(20 mg/kg simvastatin treat group), S2 group(40 mg/kg simvastatin treat group) and S3 group(60 mg/kg simvastatin treat group) and control group, 10 guinea pigs in each group. The asthmatic models were established by ovalbumin(OVA) sensitization and repeated stimulation. Serum level of IL-4 and TGF-β1 were detected by enzyme-linked immunosorbent assay(ELISA). Results Compared with the control group, the level of IL-4, TGF-β1 in the asthma model group,S1 group,S2 group and S3 group were significantly higher(P < 0.01). The level of IL-4, TGF-β1 in asthma group was higher than simvastatin treat group(P < 0.05). The level of IL-4, TGF-β1 in S1 and S3 group was higher than S2 group(P < 0.05). Conclusion Simvastatin can reduce airway inflammation by lowering the level of IL-4. Simvastatin can inhibit asthma airway remodeling by reducing the level of TGF-β1.
引文
[1]中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南(2016年版)[J].中华结核和呼吸杂志,2016,39(9):675-697.
[2]Global Initiative for Asthma.Global strategy for asthma management and prevention 2017[EB/OL].(2017-2-1)[2018-8-29].Available at:http://ginasthma.org.
[3]林江涛,王文巧,周新,等.我国30个省市城区门诊支气管哮喘患者控制水平的调查结果[J].中华结核和呼吸杂志,2017,40(7):494-498.
[4]Chung KF,Wenzel SE,Brozek J,et al.International ERS/ATS guidelines on definition,evaluation and treatment of severe asthma[J].Eur Respir J,2014,43(2):343-373.
[5]方利华.瑞舒伐他汀对冠心病合并高脂血症老年患者血脂水平和炎症因子影响的临床研究[J].中国现代医学杂志,2014,24(36):43-46.
[6]Ierodiakonou D,Postma DS,Koppelman GH,et al.TGF-1 polymorphisms and asthma severity,airway inflammation,and remodeling[J].J Allergy Clin Immunol,2013,131(2):582-585.
[7]W?sche A,SchreiberJ.Pathophysiology,diagnosis and treatment of asthma:focusing on a chronic disease[J].Anasthesiol Intensiemed Notfallmed Schmerzther,2016,51(6):392-399.
[8]Jeno WY,Shin IS,Shin HK,et al.Samsoeum water extract attenuates allergic airway inflammation via modulation of Thl/Th2cytokines and decrease of iNOS expression in asthmatic mice[J].BMCComplement Altern Med,2015,15:47.
[9]刘金凤.哮喘患儿嗜酸性粒细胞、IL-4及IFN-γ检测的临床意义[J].中国儿童保健杂志,2014,22(1):96-98.
[10]Pini L,Pinelli V,Modina D,et al.Central airways remodelingin COPDpatients[J].Int J Chron Obstruct Pulmon Dis,2014,9:927-933.
[11]Kudo M,Ishigatsubo Y,Aoki I.Pathology of asthma[J].Front Microbiol,2013,4:263.
[12]Tian X,Zhang J,Tan TK,et al.Association ofβ-catenin with P-Smad3but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1[J].J Cel Sci,2013,126(Pt 1):67-76.
[13]Schuliga M,Javeed A,Harris T,et al.Transforming growth factorβ-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2[J].Am J Respir Cell Mol Biol,2013,48(3):346-353.
[14]Halwani R,Al-Muhsen S,AI-Jahdali H,et al.Role of transforming growth factor-βin airway remodeling in asthma[J].Am J Respir Cell Mol Biol,2011,44(2):127-133.
[15]Liou CJ,Cheng PY,Huang WC,et al.Oral lovastatin attenuates airway Inflammation and mucus secretion in ovalbumin induced murine model of asthma[J].Allergy Asthma Immunol Res,2014,6(6):548-557.
[16]Krauth MT,Majlesi Y,Sonneck K,et al.Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells[J].Allergy,2006,61(3):281-288.
[17]McKay A,Leung BP,McInnes IB,et al.A novel antiinflammatory role of simvastatin in a murine model of allergic asthma[J].J Immunol,2004,172(5):2903-2908.
[2]Global Initiative for Asthma.Global strategy for asthma management and prevention 2017[EB/OL].(2017-2-1)[2018-8-29].Available at:http://ginasthma.org.
[3]林江涛,王文巧,周新,等.我国30个省市城区门诊支气管哮喘患者控制水平的调查结果[J].中华结核和呼吸杂志,2017,40(7):494-498.
[4]Chung KF,Wenzel SE,Brozek J,et al.International ERS/ATS guidelines on definition,evaluation and treatment of severe asthma[J].Eur Respir J,2014,43(2):343-373.
[5]方利华.瑞舒伐他汀对冠心病合并高脂血症老年患者血脂水平和炎症因子影响的临床研究[J].中国现代医学杂志,2014,24(36):43-46.
[6]Ierodiakonou D,Postma DS,Koppelman GH,et al.TGF-1 polymorphisms and asthma severity,airway inflammation,and remodeling[J].J Allergy Clin Immunol,2013,131(2):582-585.
[7]W?sche A,SchreiberJ.Pathophysiology,diagnosis and treatment of asthma:focusing on a chronic disease[J].Anasthesiol Intensiemed Notfallmed Schmerzther,2016,51(6):392-399.
[8]Jeno WY,Shin IS,Shin HK,et al.Samsoeum water extract attenuates allergic airway inflammation via modulation of Thl/Th2cytokines and decrease of iNOS expression in asthmatic mice[J].BMCComplement Altern Med,2015,15:47.
[9]刘金凤.哮喘患儿嗜酸性粒细胞、IL-4及IFN-γ检测的临床意义[J].中国儿童保健杂志,2014,22(1):96-98.
[10]Pini L,Pinelli V,Modina D,et al.Central airways remodelingin COPDpatients[J].Int J Chron Obstruct Pulmon Dis,2014,9:927-933.
[11]Kudo M,Ishigatsubo Y,Aoki I.Pathology of asthma[J].Front Microbiol,2013,4:263.
[12]Tian X,Zhang J,Tan TK,et al.Association ofβ-catenin with P-Smad3but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1[J].J Cel Sci,2013,126(Pt 1):67-76.
[13]Schuliga M,Javeed A,Harris T,et al.Transforming growth factorβ-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2[J].Am J Respir Cell Mol Biol,2013,48(3):346-353.
[14]Halwani R,Al-Muhsen S,AI-Jahdali H,et al.Role of transforming growth factor-βin airway remodeling in asthma[J].Am J Respir Cell Mol Biol,2011,44(2):127-133.
[15]Liou CJ,Cheng PY,Huang WC,et al.Oral lovastatin attenuates airway Inflammation and mucus secretion in ovalbumin induced murine model of asthma[J].Allergy Asthma Immunol Res,2014,6(6):548-557.
[16]Krauth MT,Majlesi Y,Sonneck K,et al.Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells[J].Allergy,2006,61(3):281-288.
[17]McKay A,Leung BP,McInnes IB,et al.A novel antiinflammatory role of simvastatin in a murine model of allergic asthma[J].J Immunol,2004,172(5):2903-2908.