Effects Of ～(188)Re Irradiation Onartery Restenosis In New Zealand White Rabbits

Objective: To evaluate the effect of beta irradiation (188Re) intravascular irradiation on inhibiting proliferation and apoptosis of rabbit vessel smooth muscle cells (VSMCs) and reducing artery restenosis after balloon angioplasty. Methods: Sixty New Zealand White rabbits, weighing 2.2～2.5 kg, were divided into two groups randomly: the control group and the irradiation group. Each group was subdivided into three groups. Each subdivided group involved 10 rabbits. In control group, balloon catheter overstretched on abdominal aorta artery to denude endothelium and then ligated femoral artery. In irradiation group, 188Re-radioactive liquid filled balloon irradiation was performed in target segment immediately after balloon overstretched injury until the accumulative radioactive dose under the irradiation surface 0.5mm was add up to 15Gy, then ligated the femoral artery. Each animal was intramuscular injected Benzyl-penicillin 40 000U perday for three days to prevent infection after operation, and fed with ordinary diet until being killed. Target segments were harvested at 1,3,6 weeks after the operation respectively. Pathologic and morphologic analysis (elastic fibers stain) included neointimal area (square millimeters), luminal area (square millimeters), luminal peridimension (millimeter), and luminal stenosis degree (%). The proliferating cell nuclear antigen (PCNA) was studied by immunohistochemical to determine the percentage of VSMCs proliferation. The percentage of VSMCs apoptosis was detected by TUNEL reaction. Blood routine was detected before and after 188Re irradiation treatment to observe whether existence bone marrow depression caused by irradiation or not. In the course of experiment, four rabbits in control group, two in irradiation group died. The remaining 54 rabbits were included in the study. Result: ① Pathologic and morphologic analysis: compare with control group in 3 weeks and 6 weeks, neointimal area of irradiation group was decreased significantly (2.11±0.17 mm2 vs 3.02±0.71 mm2,P=0.003;2.63±0.84 mm2 vs 3.80±0.99 mm2,P=0.023); luminal area was increased significantly (5.87±0.57 mm2 vs 4.96±0.64 mm2,P=0.009;4.74±0.59 mm2 vs 4.16±0.40 mm2,P=0.037); luminal peridimension enlarged significantly (4.61±0.78 mm vs 3.64±0.93 mm,P=0.040;3.85±0.65 mm vs 3.12±0.56 mm,P=0.031); lumial stenosis degree was reduced significantly (23.04±4.85 mm2 vs 33.44±6.47 mm2,P=0.003;30.82±7.18 mm2 vs 41.46±10.95 mm2,P=0.038).② PCNA analysis:In 1 week and 3 weeks, PCNA positive cells were decreased significantly in irradiation group than that in control group (27.69±7.04% vs 42.71±6.11%,P=0.0004;20.88±4.55% vs 29.48±10.13%,P=0.046), and there were no significant difference between two groups in 6 weeks (P=0.076). ③TUNEL analysis: TUNEL positive cells of irradiation group were increased significantly than that of control group (40.16±7.93% vs 28.50±9.39%,P=0.018) in 3 weeks, and there were no significant difference between two groups in 1 week and 6 weeks (P=0.212 vs P=0.251).④Blood routine analysis: There were no significant difference in the level of Red blood cell (RBC), hemoglobin(HGB), White blood cell (WBC), blood platelet (PLT) value before and after irradiation treatment(P>0.05). Conclusion: Apply 188Re to intraluminal irradiation can inhibit the proliferation of VSMCs, accelerate the apoptosis of VSMCs, decrease the neointimal area, increased the luminal area, enlarge the luminal peridimension and reduce the lumial stenosis degree respectively. Intravascular irradiation can prevention restnosis after angioplasty efficiently. 188Re is expected to be an ideal radioactive source of intravascular irradiation therapy. But our experiment should be has an advanced study, because the experiment object is rabbit abdominal aorta artery, which is difference to human coronary artery.