全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
-  2017 

转化生长因子-β 对肥胖哮喘小鼠气道重塑的影响及吡非尼酮的干预作用

DOI: doi:10.7507/1671-6205.201701037

Keywords: 哮喘, 肥胖, 重塑, 吡非尼酮, 转化生长因子 β

Full-Text   Cite this paper   Add to My Lib

Abstract:

目的 探讨转化生长因子-β(TGF-β)对肥胖哮喘小鼠气道重塑的影响及吡非尼酮干预的作用。 方法 75 只 C57BL/6J 小鼠随机分为对照组(A 组)、肥胖组(B 组)、肥胖哮喘组(C 组)、布地奈德治疗组(D 组)、吡非尼酮治疗组(E 组)5 组,每组 15 只。肥胖小鼠以高脂饮食诱导肥胖模型,C、D、E 组采用卵清蛋白致敏激发建立哮喘模型,对照组以普通饲料饲养,生理盐水致敏激发。D 组以布地奈德悬液(0.5 mg/ml)雾化,E 组以吡非尼酮(300 mg/kg)饮水干预,余组正常饮水。4 周后收集支气管肺泡灌洗液(BALF)进行细胞计数及分类。肺组织切片观察小鼠气道炎症及重塑情况,测定气管壁总面积(WAt)、气管平滑肌面积(WAm)和管腔基底膜周长(Pbm)。采用酶联免疫吸附实验、蛋白质印迹法检测 TGF-β 水平。 结果 C 组小鼠 BALF 中白细胞总数、嗜酸性粒细胞百分比、TGF-β 水平、气管壁厚度(WAt/Pbm)和平滑肌厚度(WAm/Pbm)均高于其他四组;E 组 BALF 中嗜酸性粒细胞百分比、WAt/Pbm 较 D 组减少( P 均<0.05);TGF-β 水平按照 C、D、E、B、A 组依次递减( P 均<0.05),且与 BALF 中嗜酸性粒细胞百分比呈正相关( r=0.79, P 均<0.01)。 结论 TGF-β 在肥胖哮喘小鼠气道中高表达,与气道重塑有密切关系。吡非尼酮能有效抑制 TGF-β 的表达,从而改善肥胖哮喘气道重塑

References

[1]  2. Inomata M, Kamio K, Azuma A. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis. Respir Res, 2014, 15(1): 1-14.
[2]  5. Mansoor JK, Decile KC, Giri SN, et al. Influence of pirfenidone on airway hyperresponsiveness and inflammation in a Brown-Norway rat model of asthma. Pulm Pharmacol Ther, 2007, 20(6): 660-668.
[3]  10. 韩伟, 陈凯, 唐华平, 等. 肥胖型哮喘小鼠体内氧化应激反应变化及其与气道炎症和重构的关系. 中国呼吸与危重监护杂志, 2011, 10(4): 331-334.
[4]  11. 王丽霞, 韩伟, 陈伟, 等. 辛伐他汀对肥胖哮喘小鼠气道炎症和重构的影响. 中华实用诊断与治疗杂志, 2016, 30(5): 435-438.
[5]  13. Macías-Barragán J, Sandoval-Rodríguez A, Navarro-Partida J, et al. The multifaceted role of pirfenidone and its novel targets. Fibrogenesis Tissue Repair, 2010, 3(1): 16.
[6]  14. Schaefer CJ, Ruhrmund DW, Pan L, et al. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev, 2011, 20(120): 85-97.
[7]  15. Li XZ, Feng JC, Hu CP, et al. Effects of Arkadia on airway remodeling through enhancing TGF-β signaling in allergic rats. Lab Invest, 2010, 90(7): 997-1003.
[8]  16. Sutherland ER, Goleva E, King TS, et al. Cluster analysis of obesity and asthma phenotypes. Plos One, 2012, 7(5): e36631.
[9]  17. Bottoms SE, Howell JE, Reinhardt AK, et al. TGF-β isoform specific regulation of airway inflammation and remodelling in a murine model of asthma. Plos One, 2012, 5(3): e9674.
[10]  18. Halwani R, Al-Muhsen S, Al-Jahdali H, et al. Role of transforming growth factor-beta in airway remodeling in asthma. Am J Respir Cell Mol Biol, 2011, 44(2): 127-133.
[11]  19. Panek M, Pietras T, Fabijan A, et al. The NR3C1 glucocorticoid receptor gene polymorphisms may modulate the TGF-beta mRNA expression in asthma patients. Inflammation, 2015, 38(4): 1479.
[12]  20. Lee HY, Kim IK, Yoon HK, et al. Inhibitory effects of resveratrol on airway remodeling by transforming growth factor-β/smad signaling pathway in chronic asthma model. Allergy Asthma Immunol Res, 2017, 9(1): 25-34.
[13]  22. Durrani SR, Viswanathan RK, Busse WW. What effect does asthma treatment have on airway remodeling? Current perspectives. J Allergy Clin Immunol, 2011, 128(3): 439-448.
[14]  23. Takeda Y, Tsujino K, Kijima T, et al. Efficacy and safety of pirfenidone for idiopathic pulmonary fibrosis. Patient Prefer Adherence, 2014, 8(3): 61-70.
[15]  24. 方丽萍, 辛晓峰. 支气管哮喘药物治疗对气道重塑的影响. 中华结核和呼吸杂志, 2012, 35(12): 927-929.
[16]  26. Kang HS, Rhee CK, Lee HY, et al. Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model. Korean J Intern Med, 2016, 31(6): 1150-1158.
[17]  1. ?Umetsu DT. Mechanisms by which obesity impacts upon asthma. Thorax, 2016, 72(2): 174.
[18]  3. Wang J, Yang Y, Xu J, et al. Pirfenidone inhibits migration, differentiation, and proliferation of human retinal pigment epithelial cells in vitro. Mol Vis, 2013, 19(11): 2626-2635.
[19]  4. Hirano A, Kanehiro A, Ono K, et al. Pirfenidone modulates airway responsiveness, inflammation, and remodeling after repeated challenge. Am J Respir Cell Mol Biol, 2006, 35(3): 366-377.
[20]  6. Durcan PJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri: population studies in Iowa and Louisiana. JAMA Neurol, 1988, 45(8): 875-877.
[21]  7. Han W, Li J, Tang HP, et al. Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level. Biochem Biophys Res Commun, 2017, 484(2): 396-402.
[22]  8. Chen M, Lv Z, Zhang W, et al. Triptolide suppresses airway goblet cell hyperplasia and Muc5ac expression via NF-κB in a murine model of asthma. Mol Immunol, 2015, 64(1): 99-105.
[23]  9. Dixon AE, Holguin F, Sood A, et al. An official American Thoracic Society Workshop report: obesity and asthma. Proc Am Thorac Soc, 2010, 7(5): 325-335.
[24]  12. Taguchi Y, Ebina M, Hashimoto S, et al. Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: extended analysis of phase Ⅲ trial in Japan. Respir Invest, 2015, 53(6): 279-287.
[25]  21. Jiang K, Chen HB, Wang Y, et al. Changes in interleukin-17 and transforming growth factor beta 1 levels in serum and bronchoalveolar lavage fluid and their clinical significance among children with asthma. Transl Pediatrics, 2013, 2(4): 154-159.
[26]  25. Hirota N, Martin JG. Mechanisms of airway remodeling. Chest, 2013, 144(3): 1026-1032.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133