The Mechanism Of Elastase Inhibitor On The Proliferation Of Inner Membrane After Ballon Injury

ObjectiveWe learned that ACEI can greatly inhibits the expression and activity of elastase inmedial membrane of smooth muscle cells and inhibits two active phase of proliferationof mSMC after balloon injury. This suggests that ACEI probably inhibits theproliferation and migration of artery smooth muscle cells towards inner membrane byinhibits the activity of elastase. This research is going to investigate the mechanism bywhich the elastase inhibitor inhibit the proliferation of mSMC and hypertrophy of innermembrane in animal model.MethodsWistar rats (46 total, 25 in test group, 21 in control group) are choosen. Injury theinner membrane of carotid artery with 2 Fr balloon catheter. ONO-6818 is given to testgroup, while vehicle is given to control group. The rats are killed on 2d, 3d, 5d afterinjury. Immunohistochemistry and hybridization in situ are preformed. Detect BrdU,anti-human MMP-1,MMP-9 index and elastaseⅡmRNA expression.ResultsAfter the elastase inhibitor is given, BrdU, MMP-1, MMP-9 and elastaseⅡmRNAexpression in medial layer of SMCs of test group is significantly inhibited comparedwith that in control group(p＜0.05). The value of above items of experiment group ismuch smaller than that of control group in 2, 3 and 5d after injury in media layer ofartery. ConclusionMedial SMC BrdU index of injured artery manifests a biphasic increase with 2peaks in the 2nd and 5th day. The elastase inhibitor inhibits the proliferation andmetastasize towards inner membrane by inhibiting the activity of elastase.