【Animal modeling】-Changes of matrix metalloproteinase 9 and its tissue inhibitory factor 1 in blood and tissue of hypertensive rats

  Objective: To investigate the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in serum, brain and vascular tissue of renovascular hypertensive rats (RHR), and the relationship between blood pressure and both of them. Relationship.

  Methods: Eighty male SD rats were randomly divided into RHR group (40 rats) and sham-operated group (40 rats). In the RHR group, the double-kidney-double-clamp method was used to make the hypertensive rat model, and the blood pressure was measured by the rat tail manometer. Stroke was determined according to Longa 5 scoring method and pathological results; Western blot and immunohistochemistry were used to determine the expressions of MMP-9 and TIMP-1 in brain tissue and blood vessels, and double-antibody sandwich ELISA was used to detect serum MMP-9 and TIMP-1 levels.

  Results: Compared with the sham operation group, the blood pressure of the rats in the RHR group increased significantly at 2, 4, 6, 8, 10, and 12 weeks after 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), (224 ± 20.0) vs ( 129.±9.0) mmHg, all P < 0.05]; 12 weeks after operation, the serum MMP-9 in RHR rats was higher than that in the sham-operated group [(783.4±109.79) vs (573.4±109.59) ng/mL, P < 0.05] The serum TIMP-1 in RHR rats was lower than that in the sham-operated group [(313.02±83.9) vs (976.19±191.1) pg/mL, P < 0.05]. At the same time, the expression of MMP-9 in the brain tissue and blood vessels of RHR rats was significantly higher than that in the sham-operated group (all P < 0.05), while the expression of TIMP-1 was significantly lower than that in the sham-operated group (all P < 0.05). Pearson correlation analysis showed that systolic blood pressure was positively correlated with MMP-9 levels in serum, brain and vascular tissues (r=0.557, r=0.774 and r=0.661, all P < 0.05), but negatively correlated with TIMP-1 levels Correlation (r=-0.481, r=-0.535 and r=-0.685, all P < 0.01).

  Conclusion: The expression of MMP-9 in serum, brain and vascular tissue of renovascular hypertensive rats is increased, while the expression of TIMP-1 is decreased. The change trend of the two in blood and tissue was consistent, and the increase of blood pressure was related to the increase of MMP-9 and the decrease of TIMP-1 in blood and tissue.