咪喹莫特对慢性哮喘模型小鼠肺组织中基质金属蛋白酶-9表达的影响  

Effects of Imiquimod on the Expression of MMP-9 in the Lung of Murine Models of Chronic Asthma

作　　者：朱祎娜 杜强[1] 秦湧[1] 崔进[1] 沈立[1] 蔡健康[1] 

机构地区：[1]南京医科大学第二附属医院呼吸科,江苏南京210011

出　　处：《现代生物医学进展》2013年第29期5635-5638,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年科学基金项目(81100010);江苏省卫生厅面上科研项目(H201205)

摘　　要：目的:观察Toll样受体7配体咪喹莫特对慢性哮喘小鼠模型气道重塑及肺组织中基质金属蛋白酶MMP-9表达的影响。方法:36只BALB/c小鼠按随机原则分成正常对照组、哮喘模型组、咪喹莫特组,每组12只。通过卵蛋白致敏,气道激发8周,末次激发24h后,检测各组小鼠气道反应性,HE染色观察气道炎症变化;Masson三色染色观察气道纤维化的改变;real-time PCR和western-blot分别检测肺组织中MMP-9的mRNA和蛋白表达。结果:慢性哮喘组小鼠气道炎症、气道高反应性和气道重塑较正常对照小鼠明显加重,而咪喹莫特组小鼠模型的气道炎症和气道反应性及气道重塑均较哮喘模型组小鼠减少或降低。慢性哮喘组小鼠肺组织MMP-9的mRNA和蛋白水平均较正常对照小鼠明显增加(P<0.05),而咪喹莫特治疗可显著降低哮喘小鼠肺组织MMP-9的mRNA和蛋白水平(P<0.05)。结论:咪喹莫特能够显著抑制慢性哮喘小鼠模型的气道炎症、降低气道高反应性并减轻气道重塑,这可能与其抑制MMP-9的表达有关。Objective： To observe the effects of Toll like receptor 7 ligand, Imiquimod, on the airway remodeling and the expression of matrix metallopeptidase （MMP）-9 in a murine model of chronic asthma. Methods：Thirty-six BALB/c mice were randomly divided into 3 groups, namely control group,asthma group and Imiquimod group with 12 mice in each group. BALB/c mice sensitized to ovalbumin （ OVA ） were chronically challenged with aerosolized OVA for eight weeksand 24 hours after the last OVA challenge. Pulmonary functions were measured to evaluate the resistance of expiration. The sections were stained with either hematoxylin ＆ eosin to assess the inflammatory cell infiltrates, Masson＇s trichrome to determine collagen deposition in the lungs. The mRNA of MMP-9 were measured by real time PCR. The protein expression of MMP-9 were determined by western blot. Results： All the parameters associated with airway inflammation and remodeling were increased in the OVA group, when treatment with Imiquimod, the airway inflammation, airway hyperresponsiveness （AHR） and remodeling were markedly inhibited. Imiquimod obviously attenuated the mRNA and protein expression of MMP-9. Conclusion： Imiquimod could suppress the progression of airway inflammation, AHR, and airway remodeling in a murine model of chronic asthma. Partly, the effect might be due to inhibition of the expression of MMP-9.

关 键 词：TOLL样受体 咪喹莫特 哮喘 气道重塑 基质金属蛋白酶-9 

分 类 号：Q95-3[生物学—动物学] R562.25[医药卫生—呼吸系统]