Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in lung tissue of hypercapnia rat model / 中国病理生理杂志

ABSTRACT

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 hypercapnia 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% CO_2,21% O_2,72% N_2) 7 h daily for 4 weeks. The parameters we would examine were as followarterial 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,PaCO_2=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 group B compared to group A (P<0.01). The expression of MMP-2 protein in the lung tissue of group B was lower than that in group A (P<0.01),but the expression of both MMP-9 and TIMP-1 proteins in the lung tissue in group B were higher than those in group A (P<0.01).CONCLUSION:Hypercapnia rat model is successfully reproduced by exposure of animals to the mix gas exposure (6% CO_2,21% O_2,and 72% N_2). The pulmonary artery pressure is not affected by hypercapnia. High concentration of CO_2 causes increase of NE activity and decrease in the relative content of elasticity fibre. High concentration of CO_2 causes the increase of MMP-2 protein expression and decrease in the MMP-9 and TIMP-1 protein expression.