关键词: 基质金属蛋白酶9, 组织基质金属蛋白酶抑制因子-1, 油酸, 急性肺损伤, 大鼠

Abstract: Objective To detect the levels of matrix metalloproteinases 9(MMP-9) and tissue matrix metalloproteinase inhibitor-1(TIMP-1) in plasma and lung homogenates of model rats with acute lung injury(ALI) induced by oleic acid,and to analyze the expression characteristics and clinical significance of MMP-9 and TIMP-1.Methods Twenty-four male SD rats were randomly divided into three groups:normal control group(n=8),oleic acid model control group for 2 h(n=8) and oleic acid model control group for 6 h(n=8).Oleic acid(OA,0.1 mL/kg) was given with slow tail vein injection to the rats in oleic acid model control group,while the rats in normal control group were injected with sodium chloride(0.1 mL/kg) solution.The observation and measurement indicators included the pathological changes of lung under light microscope,arterial partial pressure of oxygen(PaO₂),lung wet/dry weight ratio(W/D),the levels of MMP-9 and TIMP-1 in plasma and lung homogenates.Results ① Histomorphology of lung:Compared with normal control group,significant pathological changes of lung were seen in oleic acid model control group,including pulmonary interstitial and alveolar edema,a large amount of serous exudation,inflammatory cells,red blood cell leakage in alveolar cavity.Part of the pulmonary interstitial thickening were uniformly stained "transparent membrane" pattern.② Compared with normal control group,as 2 h and 6 h,PaO₂ of rats in oleic acid model group decreased significantly(P<0.001) while W/D increased significantly(P<0.05).③ Compared with normal control group,as 2 h and 6 h model groups,the level of MMP-9 in plasma and lung homogenates increased significantly(P<0.001) while TIMP-1 in plasma and lung homogenates decreased significantly(P<0.05,P<0.01 or P<0.001);when 2 h models were compared with 6 h models,there was no significant change(P>0.05) in MMP-9 and TIMP-1 in plasma and lung homogenate.④ In both 2 h and 6 h models,there was a highly positive correlation(r=0.999,P<0.001 or r=0.885,P<0.05) between MMP-9 in plasma and that in lung homogenate,meanwhile,there was also highly positive correlation(r=0.850,P <0.001 or r=0.800,P<0.05) between TIMP-1 in plasma with that in lung homogenate.Conclusion The level of MMP-9 in plasma and lung homogenate increased significantly while that of TIMP-1 decreased significantly in rats in oleic acid model control group,and there were no significant changes of MMP-9 and TIMP-1 with the development of ALI from 2 h to 6 h.There were highly positive correlation between plasma MMP-9,TIMP-1 and those in lung homogenates,which suggest that the detection of plasma MMP-9 and TIMP-1 may contribute to the diagnosis and treatment of ALI.

Key words: matrix metalloproteinases 9(MMP-9), tissue matrix metalloproteinase inhibitor-1(TIMP-1), oleic acid, acute lung injury(ALI), rats