基质金属蛋白酶9和血管内皮生长因子表达在大鼠肺血栓栓塞症模型肺损伤中的作用  

Role for matrix metalloproteinases-9 and vascular endothelial growth factor in progression of lung injury associated with pulmonary thromboembolism

作　　者：朱敏[1] 王辰[1] 张黎明[1] 庞宝森[1] 翟振国[1] 杨媛华[1] 牛淑洁[1] 毛燕玲[1] 马力[1] 翁心植[1] 

机构地区：[1]首都医科大学附属北京朝阳医院北京呼吸疾病研究所,100020

出　　处：《国际呼吸杂志》2008年第19期1166-1170,共5页International Journal of Respiration

摘　　要：目的通过颈外静脉注入自体血栓建立大鼠急性肺血栓栓塞症（pulmonary thromboembolism，PTE）模型，观察急性PTE后基质金属蛋白酶9（matrix metalloproteinases-9，MMP-9）和血管内皮生长因子（vascular endothelial growth factor，VEGF）的水平变化和表达，及其在PTE后肺组织病理改变中的作用。方法56只健康雄性SD大鼠随机均分为PTE组及假手术（sham）组。于制模后2h、6h、24h及72h处死大鼠。应用苏木精-伊红染色方法观察肺组织病理改变。采用酶联免疫吸附试验法测定血清及支气管肺泡灌洗液（BAI，F）中MMP-9和VEGF浓度；考马斯亮兰法测定BALF中总蛋白浓度并进行细胞计数；免疫组织化学染色观察MMP-9和VEGF在肺组织中的表达。结果①病理结果：PTE组栓塞区肺组织有肺损伤改变；sham组未见上述病理变化；②血清学结果：PTE组MMP-9和VEGF浓度在6h、24h和72h显著高于sham组（P〈0．01）；③BALF结果：PTE组MMP-9浓度24h时显著高于sham组（P〈0．01）；VEGF2h和24h均显著高于sham组（P〈O．05，P〈0．01）；PTE组BALF中总蛋白浓度和细胞数2h和24h组均显著高于sham组（P值均〈0．01）；④免疫组织化学结果：显示PTE组MMP-9和VEGF表达显著高于sham组。结论急性PTE可引起肺损伤。PTE可引起血液中MMP-9和VEGF细胞因子释放及其肺组织中显著表达，促进炎性细胞和蛋白渗出，参与PTE相关肺损伤的发生。Objective To investigate the role of matrix metalloproteinases-9 （MMP-9） and vascular endothelial growth factor （VEGF） in the progression of lung pathological alteration associated with pulmonary thromboembolism（PTE） induced by injecting thromboemboli into external jugular veins of rats. Methods Fifty-six male Sprague Dawley rats were randomly divided into PTE group and sham group. Experimental PTE models were induced by injecting emboli into external jugular veins of rats. Other animals received only saline served as shams. The rats were sacrificed at 2 h,6 h,24 h and 72 h after the models were induced. ①The histopathological evaluation was performed by haematine-eosin staining. ②Blood serum and bronchoalveolar lavage fluids（BALF） were analyzed for MMP-9 and VEGF by ELISA methods. ③The total protein and cells count in BALF were examined. ④The expressions of MMP-9 and VEGF were evaluated by immunohistochemical staining, Results ① Histopathological results., there were changes of lung injury in embolic zone. No same pathologic changes were seen in sham group. ②The detecting results of blood cytokines：the serum levels of MMP-9 and VEGF were elevated significantly in PTE group compared with those in sham rats at 6 h, 24 h and 72 h, respectively（ P〈0.01）. ③The detecting results of BALF： compared with that of shams,the level of MMP-9 in BALF elevated significantly at 24 h（ P〈0.05） ,and the level of VEGF was significantly increased at 2 h and 24 h in PTE group（ P〈0.05 ; P〈0.01 respectively）. In PTE group the total protein and cells count increased significantly at 2 h and 24 h than those of sham groups （both P〈0.01 ）. In PTE groups the serum level of MMP-9 had significant correlation with that of the total protein and cells count （ P〈0.05, P〈 0.05）.④The expression of MMP-9 and VEGF were more positively in PTE group than that of sham group in the lung parenchyma by immunohistochemical stain. Conclusions Acute PTE rat model could lead to lung injury. P

关 键 词：肺血栓栓塞症 肺损伤 基质金属蛋白酶 血管内皮生长因子 

分 类 号：R563[医药卫生—呼吸系统] R-332[医药卫生—内科学]