Expression and significance of matrix metalloproteinase-2 in plasma and aortic tissue of mice with aldosterone induced aortic dissection
Objective To observe the expression of matrix metalloproteinase-2(MMP-2)in plasma and aortic tissue of mice with aldosterone induced aortic dissection,and to investigate its relationship with aortic dissection induced by aldosterone.Methods Forty-five male C57BL/6J mice were randomly divided into control group,model group and treatment group,with 15 mice in each group.Model group and treatment group received pump of 500 μg/kg aldosterone daily,and oral administration of 0.9%NaCl+0.2%KC1 solution,totally for 4 consecutive weeks.Treatment group received spironolactone(20 mg/kg)by gavage on the next day after aldosterone pump,totally for 4 consecutive weeks.Control group received normal intaking water with no treatment.The tail blood pressure was measured before,at week 2 and at the end of modeling in three groups,respectively.ELISA was used to detect the plasma level of MMP-2 from the inner canthal vein under general anesthesia in three groups.The abdominal aortic tissues were taken after execution.HE staining and Masson staining were used to observe the morphological changes and fibrillation of the aortic tissues,and immunofluorescence method was used to detect the expression of MMP-2 protein.Results(1)There was no significant difference in the systolic blood pressure among three groups before,at week 2 and at the end of modeling(P>0.05).The diastolic blood pressure showed no significant difference before and at week 2 of modeling(P>0.05).At the end of modeling,the diastolic blood pressure showed significant difference among three groups(P<0.05),was higher in model group than that in control group and treatment group(P<0.05),and showed no significant difference between control group and treatment group(P>0.05).(2)The HE staining results showed that the aortic intima and media in model group were ruptured and damaged,leading to the formation of blood perfusion false lumens and nourishing blood vessels.The aortic tissues in control and treatment groups were basically normal.The Masson staining results showed collagen deposition throughout the entire aorta of model group,with disordered arrangement of elastic fibers;significantly decreased collagen deposition in the blood vessels of treatment group;a compact aortic structrue and continuous collagen fibers in control group.(3)The levels of MMP-2 in plasma and the expression of MMP-2 protein in aortic tissue were higher in model group[(0.29±0.13)ng/L,37.79±2.28]than those in control group[(0.26±0.14)ng/L,26.90±2.86]and treatment group[(0.26±0.01)ng/L,29.32±2.48](P<0.05),and showed no significant difference between control group and treatment group(P>0.05).Conclusions The MMP-2 expression is upregulated in the mice models with aldosterone induced aortic dissection,and the aortic tissues are damaged.The MMP-2 expression is downregulated after antagonizing aldosterone,and the aortic pathological changes are improved.MMP-2 may be involved in the aortic dissection caused by aldosterone.
aortic dissectionaldosteronespironolactonematrix metalloproteinase-2C57BL/6J male mice