基质金属蛋白酶及其抑制物在高碳酸血症大鼠肺组织中的表达  

Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in lung tissue of hypercapnia rat model

作　　者：何耀红[1,2] 王辰[1] 庞宝森[1] 李立宇[1] 邝土光[1] 

机构地区：[1]首都医科大学北京朝阳医院呼吸疾病研究所,北京100038 [2]首都医科大学附属复兴医院,北京100038

出　　处：《中国病理生理杂志》2010年第1期116-121,共6页Chinese Journal of Pathophysiology

摘　　要：目的:观察单纯高碳酸血症大鼠模型的血清中性粒细胞蛋白酶(NE)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和金属蛋白酶组织抑制剂(TIMP-1)的活性,以及它们在肺组织中的表达,探讨高浓度二氧化碳(CO2)引起肺组织损伤的机制。方法:雄性Wistar大鼠40只,随机分为正常对照组(A组,20只大鼠)、高碳酸血症组(B组,20只大鼠)。B组大鼠置于高CO2舱中,并向舱中匀速输入6%CO2混合气体(6%CO2,21%O2,73%N2),每天7h,连续4周,完成大鼠高碳酸血症模型的复制。用ELISA法测定大鼠血清MMP-2、MMP-9、TIMP-1活性及NE活性;弹力纤维染色标本进行弹性纤维相对含量的测定;免疫组化方法检测肺组织中MMP-2、MMP-9及TIMP-1的表达及光镜下进行病理学观察。结果:B组大鼠血清MMP-2、MMP-9、TIMP-1活性与A组之间并无显著差异(P>0.05);B组大鼠NE活性明显高于A组(P<0.01);光镜下可见B组大鼠肺泡壁明显增厚,肺微血管内皮细胞损伤,小静脉扩张,血栓形成;小动脉内皮细胞肿胀,管腔狭窄,血管周围有袖套状水肿区;并可见小灶性肺实质出血;A组大鼠弹力纤维呈束状,连续无断裂;B组大鼠可见弹力纤维断裂降解,且肺组织中弹力纤维的含量较A组明显减少(P<0.01);B组大鼠肺组织中MMP-2的表达明显低于A组(P<0.01);而肺组织中MMP-9及TIMP-1的表达B组大鼠明显高于A组(P<0.01)。结论:通过复制出常压、常氧、单纯高碳酸血症动物模型;单纯的PaCO2增高对肺动脉压无明显影响;高浓度CO2可以使NE活性明显增高,使弹性蛋白的降解增多,肺组织弹性纤维断裂降解,数量减少;在单纯高碳酸血症动物模型中,MMP-2的表达明显降低,MMP-9及TIMP-1在肺组织中表达明显增高,导致肺损伤。AIM ： To study the expression of matrix metalloproteinase - 9 （ MMP - 9 ）, matrix metalloproteinase - 2（ MMP - 2） and the tissue inhibitor of metalloproteinase（ TIMP - 1 ） in the lung tissue of the hypereapnia rat. METHODS： Forty Wistar rats were randomly divided into a control group （group A, n =20） and hypercapnia group （group B, n =20）. Group B received mix gas exposure （6% CO2, 21% 02, 72% N2 ） 7 h daily for 4 weeks. The parameters we would examine were as follow： arterial blood gas; the mean pulmonary artery pressure;MMP -2, MMP -9, TIMP - 1, and NE activity in lung tissue. Masson pigmentation of elasticity fibre was analyzed by computer image analyzer. Histopathological changes of lung tissue were observed under light microscope. The protein expression of MMP （ MMP - 2, MMP - 9） and TIMP （TIMP - 1 ） in lung tissue were determined by immunocytochemistry. RESULTS ： Decompensate respiratory acidosis （pH =7.20 ±0. 04, PaCO2 =7.84 ±0.15） developed in group B. The mean pulmonary artery pressure were similar between groups B and A （P 〉 0. 05 ）. Tissue edema in the lung, endothelial cell damage of the small blood vessels, pulmonary micro thrombus formations and increased pulmonary capillary permeability were observed in group B. NE activity increased significantly （ P 〈 0. 01 ）. However, no significant change of MMP - 2, MMP - 9, TIMP - 1 activity was found in group B and group A （ P 〉 0. 05 ）. There was significant decrease in the relative content of elasticity fibre in lung tissue in

关 键 词：肺疾病 慢性阻塞性 高碳酸血 基质金属蛋白酶 

分 类 号：R563[医药卫生—呼吸系统]