Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma

LI Wen-Kai; LI Yun; ZHONG Li-Li

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Chinese Journal of Contemporary Pediatrics ›› 2011, Vol. 13 ›› Issue (10) : 827-831.

EXPERIMENTAL RESEARCH

Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma

LI Wen-Kai, LI Yun, ZHONG Li-Li

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Abstract

OBJECTIVE: To study the effects of all-trans retinoic acid (ATRA) on airway responsiveness, airway remodeling and expression of matrix metalloproteinase-9 (MMP-9) protein in rats with asthma. METHODS: Forty rats were randomly divided into five groups: asthma model, normal saline (control), ATRA treatment, cotton oil treatment and budesonide treatment (n=8 each). Asthma was induced by ovalbumin sensitization and challenge in the asthma model, and the ATRA, cotton oil or budesonide treatment groups. ATRA (50 μg/kg), cotton oil (1 mL) or budesonide (0.32 mg/kg) was administered before ovalbumin challenge in the three treatment groups. Airway responsiveness was assessed. The lung tissues were sampled to detect airway remodeling and the expression of MMP-9 protein by immunohistochemistry. RESULTS: The expression of MMP-9 in lung tissues in the ATRA treatment group was significantly higher than that in the control group, but the airway responsiveness in the ATRA treatment group was not significantly different from that in the control group. The airway responsiveness and the expression of MMP-9 in lung tissues were significantly reduced in the ATRA treatment group compared with the asthma model group. The airway remodeling was significantly improved in the ATRA treatment group compared with the asthma model group. CONCLUSIONS: ATRA may alleviate airway hyperresponsiveness and airway remodeling possibly through decreasing the protein expression of MMP-9 in rats with asthma.

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Asthma / All-trans retinoic acid / Airway responsiveness / Airway remodeling / Rats

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LI Wen-Kai, LI Yun, ZHONG Li-Li. Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma[J]. Chinese Journal of Contemporary Pediatrics. 2011, 13(10): 827-831

References

［1］金红芳, 方红, 王宏伟. 全反式维甲酸抗支气管哮喘大鼠气道炎症的作用及机制［J］. 中华结核和呼吸杂志, 2004, 9(27): 67-68.

［2］Locke NR, Royce SG, Wainewright JS, Samuel CS, Tang ML. Comparison of airway remodeling in acute, subacute, and chronic models of allergic airways disease［J］. J Immunol, 2006, 176(11):6553-6559.

［3］刘珊珊, 贺湘玲, 钟礼立. 哮喘大鼠8异前列腺素F2α水平变化的实验研究［J］. 医学临床研究, 2008, 25(5): 881-882.

［4］Temelkovski J, Hogan SP, Shepherd DP, Foster PS, Kumar RK. An improved murine model of asthma:selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen［J］. Thorax, 1998, 53(10):849-856.

［5］Shen H, O′Byrne PM, Ellis R, Wattie J, Tang C, Inman MD. The effects of intranasal budesonide on allergen-induced production of interleukin-5 and eotaxin, airways, blood, and bone marrow eosinophilia, and eosinophil progenitor expansion in sensitized mice［J］. Respir Crit Care Med, 2002, 166(2):146-153.

［6］Yamauchi K, Inoue H. Airway remodeling in asthma and irreversible airflow limitation-ECM deposition in airway and possible therapy for remodeling ［J］.Allergol Int, 2007, 56(4):321-329.

［7］Ohbayashi H, Shimokata K. Matrix metalloproteinase-9 and airway remodeling in asthma［J］. Curr Drug Targets Inflamm Allergy, 2005, 4(2):177-181.

［8］Vignola AM, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, et al. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis［J］. Respir Crit Care Med, 1998, 158(6):1945-1950.

［9］Atkinson JJ, Senior RM. Matrix metalloproteinase-9 in lung remodeling［J］. Respir Cell Mol Biol, 2003, 28(1):12-24.

［10］Araujo BB, Dolhnikoff M, Silva LF, Elliot J, Lindeman JH, Ferreira DS, et al. Extracellular matrix components and regulators in the airway smooth muscle in asthma［J］. Eur Respir J, 2008, 32(1):61-69.

［11］Margulis A, Nocka KH, Brennan AM, Deng B, Fleming M, Goldman SJ, et al. Mast cell-dependent contraction of human airway smooth muscle cell-containing collagen gels: influence of cytokines, matrix metalloproteases, and serine proteases［J］. J Immunol, 2009, 183(3): 1739-1750.

［12］Dolhnikoff M, da Silva LF, de Araujo BB, Gomes HA, Fernezlian S, Mulder A, et al. The outer wall of small airways is a major site of remodeling in fatal asthma［J］. Allergy Clin Immunol, 2009, 123(5): 1090-1097.

［13］Mookerjee I, Hewitson TD, Halls ML, Summers RJ, Mathai ML, Bathgate RA,et al. Relaxin family peptide receptor-1 protects against airway fibrosis during homeostasis but not against fibrosis associated with chronic allergic airways disease［J］. Endocrinology, 2009, 150(3):1495-1502.

［14］孔祥永, 栾斌, 贾天明, 冯建飞, 王秀芳, 王西阁, 等.地塞米松对实验性哮喘大鼠气道细胞DNA合成和气道重塑的影响［J］. 中国当代儿科杂志, 2002, 4(2): 81-83.