MMP-9和TIMP-1在大鼠肺气肿模型细胞外基质重塑中的作用

Role of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Extracellular Matrix Remodeling in Rat Model of Chronic Obstructive Pulmonary Emphysema

目的 研究基质金属蛋白酶 -9(MMP -9)和金属蛋白酶组织抑制因子 -1(TIMP -1)在大鼠肺气肿模型肺组织中的表达及在细胞外基质重塑中的作用。方法 建立吸烟肺气肿大鼠模型 ,70只雄性Wistar大鼠 ,随机分为对照组 ( 10只 )和吸烟 1至 6月组 (每组 10只 ) ,用原位杂交和免疫组化等方法观察肺组织MMP -9和TIMP -1的mRNA及蛋白的表达 ,用免疫组化法观察IV型胶原在肺内的表达。结果 与对照组相比 ,吸烟组肺组织MMP -9、TIMP -1mRNA及蛋白的表达均明显上升 (P <0 0 5 ) ;吸烟组肺组织MMP -9mRNA及蛋白的表达逐渐上升 ,至吸烟 6月时达高峰 ;而TIMP -1mRNA及蛋白的表达渐上升 ,至吸烟 3、4月时达高峰 ,后逐步下降 ;IV型胶原的表达在吸烟 3月时达高峰 ,然后渐降。结论 肺组织MMP -9/TIMP -1的动态平衡在吸烟大鼠肺气肿模型细胞外基质重塑中产生重要作用。

Objective To study the role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in extracellular matrix remodeling in rat model of chronic obstructive pulmonary emphysema .Methods Seventy Wistar rats were randomly subdivided into the control group and the smoking groups which were randomly subdivided into one month to six month smoking group again.The smoking groups were exposed to cigarette smoke for one to six months, The expressions of MMP-9 and TIMP-1 mRNA and proteins in lung tissue were detected by in situ hybridization and immunohistochemistry respectively.In lung tissue the expression of collagen Ⅳ was assessed by method of immunohistochemistry.Results Compared with the control group,the expressions of MMP-9 and TIMP-1 mRNA and proteins in lung tissue from the smoking groups were remarkable elevated(P<0 05); The expression of MMP-9 in lung tissue in smoking groups was increased gradually, till to the peak in the six month smoking group;but the expression of TIMP-1 was increased gradually,to the peak in the three and four month smoking groups,then decreased slowly;In lung tissue the expression of collagen Ⅳ was increased, ,to the peak in the three month smoking groups,then decreased gradually.Conclusions The dynamic balance of MMP-9 and TIMP-1 could play an important role in extracellular matrix remodeling in rat model of smoking-induced pulmonary emphysema.