老龄大鼠肺内基质金属蛋白酶2、9及基质金属蛋白酶组织抑制因子1、2、3表达变化  

Changes of matrix metalloproteinase 2,9 and tissue inhibitor of metalloproteinase1,2,3 expression level in aged rat lung

作　　者：赵志杰[1] 刘新民[1] 周国鹏[1] 卜定方[1] 李雪迎[1] 宗丽丽[1] 李江[1] 

机构地区：[1]北京大学第一医院老年科,北京100034

出　　处：《北京大学学报（医学版）》2008年第1期101-104,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金项目资助(30300394)~~

摘　　要：目的:对比观察老龄大鼠和成年大鼠肺胶原蛋白的改变、转化生长因子β(transforming growth factor β,TGF-β)水平的变化、基质金属蛋白酶(matrix metalloproteinases,MMPS)MMP2,MMP9以及基质金属蛋白酶组织抑制因子(tissue inhibitor of metalloproteinases,TIMPS)表达调控的变化,寻找肺间质纤维化发病率随年龄增加的可能原因。方法:通过羟脯氨酸定量测定肺组织胶原含量,ELISA方法测定TGF-β1蛋白水平,荧光定量PCR(realtime PCR)技术测定MMP2,MMP9,TIMP1,TIMP2,TIMP3 mRNA表达量的变化。结果:与成年大鼠组相比,老龄大鼠肺细胞外胶原成分增加,TGF-β1蛋白水平升高[(756±160)pg/gvs(1000±246)pg/g,P<0.05],MMP2 mRNA(3.15±1.76vs0.17±0.13,P<0.01)表达水平降低,MMP9 mRNA(1.66±0.67vs1.74±0.87,P>0.05)表达水平没有明显变化。老龄大鼠组TIMP1 mRNA(2.00±1.74vs0.11±0.06,P<0.01),TIMP2 mRNA(7.60±2.51vs2.69±1.76,P<0.01),TIMP3 mRNA(1.32±0.46vs0.29±0.16,P<0.01)表达水平均低于成年大鼠组。结论:肺老化后细胞外胶原比例增加,TGF-β1蛋白水平升高,MMP2和MMP9转录水平改变,TIMPS mRNA转录水平降低等多重因素共同构成肺间质纤维化发病率随年龄增加的基础。Objectives： To investigate the underlying mechanism of age related increase of pulmonary fibrosis incidence. Methods： The levels of pulmonary collagen and TGF-β1 protein, MMP2,9 mRNA and TIMP 1,2,3 mRNA expression were measured by ELISA and reahime PCR. Results： As compared with adult rats [ （756 ± 160） pg/g vs （ 1 000± 246 ） pg/g, P 〈 0.05 ] the aged rats had more extracellular matrix components, increased TGF-betal protein level, lower （3.15 ± 1.76 vs 0. 17 ±0.13, P 〈0.01 ） MMP2 mRNA expression and TIMP 1,2,3 mRNA expressions （TIMP1 2.00 ± 1.74 vs 0.11 ± 0.06, TIMP2 7.60 ±2.51 vs 2.69 s 1.76, TIMP3 1.32 s0.46 vs 0. 29 ±0. 16, P 〈0.01 ）. No difference was observed in MMP9 （ 1.66 ± 0.67 vs 1.74 ±0.87, P 〉 0.05 ） mRNA expression. Conclusion： elevation in TGF-betal protein level, changes in the expression of MMP2/9 and decreased expression of TIMPS mRNA could be the underlying mechanism of age related increase of pulmonary incidence.

关 键 词：衰老 肺纤维化 转化生长因子β 明胶酶类 金属蛋白酶类组织抑制剂 

分 类 号：R563.13[医药卫生—呼吸系统]