| Objective To evalvate the effects of endovascular irradiation associated with simvastatin and clopidogrel on restenosis after interveneional therapy ,and investigate the possible mechanism of restenosis prevention after endovascular irradiation associated with simvastatin and clopidogrel . Methods 72 male New Zealand white rabbits were studied.6 rabbits were fed on normal diet ,these rabbits were normal control group(A group). 66 rabbits have been fed on a cholestetol-enriched diet to become athetoscletosis modle. These rabbits were randomized into 4 groups: injured group(B group),medicine group(C group), irradiated group(D group) , associated group(E group).Except A group,the other rabbits must be performed ballon injury on right iliac artery. After injured,D group,E group were followed immediately by ionizing radiation using liquid 32P-filled ballon catheter;The rabbits in C group and E group were fed with simvastatin(15mg/d) and clopidogrel(50mg/d) each day. The proliferation of vascular cells was evaluated by means of immunohistochemistry of proliferation of cellular nuclear antigen (PCNA).Meanwhile immunohistochemistry method was used to detect the expression of α-Smooth Muscle actin(α-SM actin) and matrix metalloproteinase 2(MMP2) in the vascular.Pathological sections of iliac artery were observed to estimated the changes of vascular histomorphology by computer analysis of photomicrogram.The expression of α-Smooth Muscle actin,PCNA and MMP2 were analyzed by image analysis.All these collected data were analyzed using factorial ANOVA. Cellular ultramicrostructure were observed by using transmission electron microscope. Results 1 14 days after injury, histopathologic analysis exhibited lumen area of injuried arteries was significantly decreased, intoma area was significantly increased respectively(p<0.05).arteries from B group displayed degenerated smooth muscle cells and fibroblasts of active function by transmission electron microscopy. 2 E group,D group,C group compared with B group:(1) 56 days after injury,morphometric analysis indicated that the lumem area was significantly larger than in injuried vessels(P<0.05),with neointima area smaller (p<0.05),these changes appear according to this order :E group> group>C group .(2) 14 days,28 days ,56 days after injury,the expression of MMP2 in the iliac arteries decreased remarkably ( p<0.05), 14 days after injury,the expression of MMP2 of four groups compared with each other: comparison of C group and D group is P>0.05,the other comparisons are all p<0.05; 28 days after injury,the comparison of every two groups is same as those of 14 days after injury. 56 days after injury,there were no significant expression of MMP2 in all groups. (3) 14 days,28 days after injury,the expression of α-SMactin in vessels decreased remarkably(p<0.05), in the same day ,the order is B group>Cgroup> group> group; 56 days after injury , the expression of α-SMactin is in the adventitia.the order is B group> C group>D group>E group, p<0.05;(4)14 days, 28 days,56 days after injury,cell proliferation was significantly reduced (p<0.05), 14 days,28days after injury,the comparisons of every two groups are: p<0.05; 56 days after injury, the comparison of C group and D group is p>0.05,the other comparisons of every two groups are same: p<0.05.Conclusion 1)The experimental restenosis-like model can established using overstretch balloon to injury the iliac artery of cholestetol-enriched diet rabbit. 2) Simvastatin and clopidogrel can prevent restenosis after balloon injury. 3)32P irradiation associated with Simvastatin and clopidogrel can prevent restenosis after balloon injury. Compared with single medicine or irradiation, 32P irradiation associated with Simvastatin and clopidogrel is the best way to prevent restenosis.4)Its mechanism might be the inhibition on neointima,through inhibiting cell proliferation and inducing cell apoptosis,and improvement on vascular remodeling, through inhiditing the expression of MMP2 and а-Smactin in the adventitia. The other mech...
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