地塞米松调节基质金属蛋白酶-2对哮喘大鼠气道重建的影响  

Modulation of Matrix Metalloproteinase by Dexamethasone in Airway Remodeling in Asthmatic Rats

作　　者：袁益明[1] 王曾礼[2] 董碧蓉[1] 

机构地区：[1]四川大学华西医院老年科,成都610041 [2]四川大学华西医院呼吸科

出　　处：《四川大学学报（医学版）》2003年第4期680-683,共4页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金 (批准号 3 9770 3 40 )资助

摘　　要：目的　观察地塞米松对气道重建的影响 ,并探讨基质金属蛋白酶 - 2 (MMP- 2 )与金属蛋白酶组织抑制物 - 1(TIMP- 1)间的平衡在其中的作用。方法　 30只雄性 Wistar大鼠随机分为哮喘组、地塞米松组和对照组 ,每组10只。动物处死后行支气管肺泡灌洗 ,收集灌洗液作细胞学检查。肺组织作病理切片 ,HE染色 ,采用计算机图象分析技术测定支气管基底膜周径 (Pbm ) ,总管壁面积 (WAt) ,内壁面积 (WAi) ,平滑肌面积 (WAm )等反映气道壁厚度的指标。半定量逆转录聚合酶连反应 (RT- PCR)技术分析肺组织中 MMP- 2与 TIMP- 1m RNA的表达。结果　 1哮喘组 WAt/ Pbm,WAi/ Pbm及 WAm / Pbm (分别为 2 5 .3± 2 .1μm2 /μm ,2 0 .4± 2 .3μm2 /μm ,4 .2± 2 .0μm2 /μm )与对照组 (2 0 .8± 1.3μm2 / μm,15 .3± 2 .1μm2 / μm,3.1± 1.1μm2 / μm)比较 ,差异有显著性 (P<0 .0 1) ,对照组与地塞米松组 (2 1.3± 2 .4 μm2 / μm,14 .2± 2 .5 μm2 / μm,3.2± 1.0 μm2 / μm)比较 ,差异无显著性 (P>0 .0 5 )。2哮喘组的MMP- 2及 TIMP- 1m RNA水平 (0 .6 8± 0 .14 ,0 .5 6± 0 .10 )与对照组 (0 .14± 0 .0 3,0 .11± 0 .0 5 )比较 ,差异有显著性 (P<0 .0 1) ,哮喘组与地塞米松组 (0 .37± 0 .11,0 .31± 0 .10 )Objective To observe the effect of dexamethasone on airway remodeling and to explore the significance of the balance between matrix metalloproteinase and the tissue inhibitor of metalloproteinase. Methods Thirty male Wistar rats were randomly divided into asthmatic group ( n =10), dexamethasone group ( n =10) and control group ( n =10). Lung tissues were sliced and stained with H.E. The parameters such as bronchial basement membrane perimeter(Pbm), total bronchial wall area(WAt), inner wall area(WAi) and smooth muscle area(WAm), which reflect the thickness of airway wall, were measured by image analysis system. The expression levels of MMP 2 and TIMP 1 mRNA in the lungs were assessed by semiquantitative reverse transcription polymerase chain reaction. Results ① WAt/Pbm, WAi/Pbm and WAm/Pbm in asthmatic group (25.3±2.1 μm 2/μm, 20.4±2.3 μm 2/μm, 4.2±2.0 μm 2/μm, respectively) were significantly higher than those in control group (20.8±1.3 μm 2/μm, 15.3±2.1 μm 2/μm, 3.1±1.1 μm 2/μm)( P <0.01). The differences between those in control group and those in dexamethasone group (21.3±2.4 μm 2/μm, 14.2±2.5 μm 2/μm, 3.2±1.0 μm 2/μm) were not statistically significant ( P >0.05). ② MMP 2 and TIMP 1mRNA levels in asthmatic group (0 68±0 14, 0.56±0.10) and dexamethasone group (0.37±0.11,0.31±0.10) were significantly higher than those in control group (0.14±0.03,0.11±0.05). The differences between asthmatic group and dexamethasone group were also significant( P <0.01). ③ There was a significant positive correlation between MMP 2 and TIMP 1 mRNA in control group and dexamethasone group ( r =0.67,0.58, P <0.05), but not in asthmatic group ( r =0 24, P >0.05). Conclusion Dexamethasone could prevent airway remodeling by downregulating the expression of MMP 2 and TIMP 1 and restoring the balance between MMP 2 and TIMP 1.

关 键 词：哮喘 气道重建 地塞米松 基质金属蛋白酶 金属蛋白酶组织抑制物 大鼠 

分 类 号：R562.25[医药卫生—呼吸系统]