Changes of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1in serum and tissues in hypertensive rats / 中国实验动物学报

ABSTRACT

Objective To investigate the expressions of metalloproteinase-9(MMP-9)in serum,brain and aorta matrix and tissue inhibitor of metalloproteinase-1(TIMP-1) in renovascular hypertensive rats(RHR),and to evaluate the association between blood pressure and levels of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1).Methods Eighty healthy male SD rats were randomly divided into RHR group(n=40) and sham-operated group(n=40).Hypertension was induced by two-kidney,two-clip(2K-2C)clamps.Systolic blood pressure(SBP) was measured every 2 weeks during 12 weeks using a tail pressure meter.Stroke was confirmed by Longa's five-point scale and pathological examination.The expressions of MMP-9 and TIMP-1 in the brain and aorta tissues were detected by Western blot and immunohistochemistry.The levels of serum MMP-9 and TIMP-1 were measured by double-antibody sandwich enzyme-linked immunosorbent assay(DAS-ELISA).Results Compared with the sham-operated group,SBP stayed significantly elevated in the RHR group at 2,4,6,8,10 and 12weeks after the operation [(157±9.0) vs.(128±7.0),(176±10.0) vs.(122±6.0),(194±8.0)vs.(117±6.5),(202±12.0)vs.(124±8.0),(218±15.0) vs.(126.±8.5),and(224±20.0)vs.(129.±9.0) mm Hg,all P< 0.05].12 weeks after the surgery,the level of serum MMP-9 in the RHR group was kept significantly higher than that in the sham-operated group [(783.4±109.79)vs.(573.4±109.59) ng/mL,P<0.05],and the serum TIMP-1 level was lower in the RHR group than that in the sham-operated group[(313.02±83.9) vs.(976.19±191.1) pg/mL,P<0.05].MMP-9 expressions were significantly higher in the brain and aorta in the RHR group than that in the sham-operated group(both P<0.05),and TIMP-1 expressions were lower than that in the sham-operated group(both P<0.05).The Pearson correlation analysis showed that MMP-9 levels in serum,brain and aorta were positively correlated with systolic blood pressure(r=0.557,r=0.774 and r=0.661,all P<0.05),and TIMP-1 levels were negatively correlated with systolic blood pressure(r=-0.481,r=-0.535 and r=-0.685,all P<0.01).Conclusions Hypertension induces increased MMP-9 and decreased TIMP-1 in serum,brain and aorta in renovascular hypertensive rats.There are consistent alterations of circulating and tissue MMP-9 and TIMP-1 levels in renovascular hypertensive rats.There is a relationship between increased blood pressure and high MMP-9 and low TIMP-1 in serum and tissues.