Effect Of MMP-2/TIMP-2 Expression On Intimal Proliferation In Rat Transplant Vasculopathy

OBJECTIVE: We investigate the role of MMP-2/ TIMP-2 in intimal proliferation in rat transplant vasculopathy.METHODS: Seventy-two SD rat were randomly divided into three groups,transplantation group(group A),the allogeneic transplantation group(group B),and the allograft with triptolide group(TP group)to establish a graft model.Each group was subdivided into 4 subgroups,and the graft arteries were obtained at 1 week,2 weeks,4 weeks,and 8 weeks after surgery,and pathological paraffin sections were made.The thickness of the graft vessel wall at each time point was measured after HE staining,and the pathological changes of each layer of the vessel wall were observed.Immunohistochemical staining was performed on each section to observe changes in MMP-2,TIMP-2,NF-?B p65,and MMP-2/TIMP-2 in the graft.RESULTS: The thickness of intima had statistically significant difference between group A and group B(p<0.05)after 1 week operation.There was no significant difference between group B and group TP.The thickness of the three groups of vessel intima at 2?4 and 8 weeks after operation were different,and the difference was statistically significant(p<0.05).The increase of vessel intima thickness in group A was the smallest,and the thickness of vessel intima in group B was the most obvious.The increase in vessel intima thickness in the TP group is somewhere in between.The expression of MMP-2 was the weakest in the vascular wall of group A,and the expression in TP group was slightly stronger than that in group A.The expression of group B was significantly higher than that in group B.The difference between the three groups was statistically significant(p< 0.05).The expression of MMP-2 in each group reached a peak between 2 weeks and 4 weeks,and then gradually decreased.TIMP-2 expression: TIMP-2 expression was the weakest in the blood vessel wall of group B,and higher in group A and TP group.At 1 week,2 weeks,and 4 weeks,group B was different from group A and group TP(p<0.05).There was no significant difference between the A group and the TP group at each time point(p>0.05).The expression of TIMP-2 in group B grew the slowest,and the growth of group A and TP group was faster,peaked in about 2 weeks to 4 weeks,and then gradually decreased.NF-?B p65 expression: NF-?B p65 expression was the strongest in group B,and weakest in group A,and higher in group TP than in group A.At each time point,group B was different from group A and group TP(p<0.05).There was a difference between the A group and the TP group at 1 week(p<0.05),and there was no significant difference(p>0.05).The expression of NF-?B p65 was the fastest in group B,and the growth in group A and TP was slower,reaching a peak in about 1 week and then gradually decreasing.The MMP-2/TIMP-2 ratio was the largest in group B,the smallest in group A,and the TP group was slightly larger than group A.At each time point,the MMP-2/TIMP-2 ratio between group B and group A and TP group was different(p<0.05).There was a difference between the A group and the TP group at 1 week(p<0.05),and there was no significant difference(p>0.05).The ratio of MMP-2/TIMP-2 in group B was the largest,and there was no significant change at each time point.There was no significant change between group A and TP group.Conclusion: 1.Increased expression of MMP-2 may participate graft intimal thickening.2.The imbalance of MMP-2/TIMP-2 ratio,the relative amount of MMP-2 may be an cause of graft intimal thickening.3.NF-?B /MMP-2 signaling pathway may be involved in the process of graft intimal proliferation.