甲泼尼龙对哮喘模型MMP-9的表达及对气道炎症的影响  

Effects of methylprednisolone on expression of MMP-9 and airway inflammation in murine models of asthma

作　　者：章剑[1] 朱建明[1] 白建文[1] 林闽加[1] 许淑敏[1] 

机构地区：[1]同济大学东方医院急危重科,上海200120

出　　处：《上海交通大学学报（医学版）》2009年第5期539-542,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市浦东新区社会发展局卫生科技项目(PW2005A-9)~~

摘　　要：目的探讨甲泼尼龙(MP)对哮喘小鼠基质金属蛋白酶-9(MMP-9)表达和气道炎症的影响。方法30只BALB/c雌性小鼠,按随机数字表法分为哮喘组、MP治疗组和生理盐水对照组,每组10只。采用鸡卵清白蛋白(OVA)腹腔注射和滴鼻的方法建立小鼠急性哮喘模型,HE染色观察肺组织病理学改变,并进行支气管肺泡灌洗液(BALF)细胞计数。采用免疫组化法和明胶酶谱法测定MMP-9蛋白的表达;RT-PCR法测定MMP-9 mRNA的表达。结果哮喘组病理切片显示明显的气道痉挛,大量炎性细胞浸润,BALF细胞计数中嗜酸性粒细胞明显增高,与对照组比较差异均有统计学意义(P<0.01);而MP治疗组病理切片显示气道痉挛程度和炎性细胞浸润均减轻,BALF中嗜酸性粒细胞减少,与哮喘组比较差异均有统计学意义(P<0.05)。免疫组化和明胶酶谱分析均显示哮喘组较对照组MMP-9蛋白表达明显增加。RT-PCR结果显示,哮喘组MMP-9 mRNA表达增多,而MP治疗组较哮喘组表达降低。结论MMP-9在哮喘小鼠肺组织中表达增高可能是导致哮喘急性炎症的机制之一。MP也可能通过抑制MMP-9表达抑制哮喘的炎症反应。Objective To investigate the effects of methylprednisolone （MP） on the expression of matrix metalloproteinase （MMP）-9 and airway inflammation in murine models of asthma. Methods Thirty female BALB/c mice were randomly divided into asthma group, MP group and control group （ n = 10）. Murine models of acute asthma were established by ovalbumin （OVA） via peritoneal injection and intranasal instillation. The pathological changes of lung tissues were observed with HE staining, and cell quantitation was conducted in bronchalveolar lavage fluid （BALF）. The expression of MMP-9 protein was determined by immunohistochemistry and gelatin zymogram, and the expression of MMP-9 mRNA was detected by RT-PCR. Results Compared with control group, there were more significant airway spasm and more infiltration of inflammatory cells in histologic examination, and there was higher eosinophil cell quantitation in BALF in asthma group （P 〈 0.01）. Compared with asthma group, there were less airway spasm and less infiltration of inflammatory cells in histologic examination, and there was lower eosinophil ceil quantitation in BALF in MP group（ P 〈 0.05）. It was revealed by immunohistochemistry and gelatin zymogram that the expression of MMP-9 protein was higher in asthma group than that in control group. It was indicated by RT-PCR that the expression of MMP-9 mRNA was increased in asthma group, while there was less expression in MP group than in asthma group. Conclusion The increased expression of MMP-9 in lung tissues of murine models of asthma may be one of the mechanisms for inflammation of asthma. MP may inhibit the inflammation of asthma through suppressing the expression of MMP-9.

关 键 词：哮喘 基质金属蛋白酶-9 甲泼尼龙 

分 类 号：R562.25[医药卫生—呼吸系统] Q786[医药卫生—内科学]