缬沙坦涂层支架对实验兔血管局部内膜增生及血管紧张素Ⅱ2型受体表达的影响

The effect of valsartan eluting-stent on the neo-intima and expression of angiotensin Ⅱ type 2 receptor in experimental rabbits

目的评价缬沙坦涂层支架对血管新生内膜及其血管紧张素Ⅱ2型受体(AT2R)表达的影响,探讨缬沙坦涂层支架防治支架内再狭窄的效果及其可能机制。方法采用多层涂布技术制备缬沙坦涂层支架和载体涂层支架。依据腹主动脉置入支架的类型将15只新西兰大白兔分为裸支架组、载体涂层支架组及缬沙坦涂层支架组,每组5只。术前、术后即刻及支架置入3个月后分别行腹主动脉造影,使用定量冠状动脉造影(QCA)软件测量血管直径及其狭窄百分数。3个月后处死实验兔,将支架血管段切片行HE染色,分别测定并比较三组支架血管段的管腔面积、内外弹力膜围绕面积、新生内膜面积及最大内膜厚度;用免疫组化法检测AT2R蛋白质表达,用RT-PCR方法测定AT2RmRNA表达。结果裸支架组、载体涂层支架组、缬沙坦涂层支架组QCA测量的术前、术后即刻及3个月后支架血管段腹主动脉平均直径差异无统计学意义。裸支架组、载体涂层支架组与缬沙坦涂层支架组的平均管腔面积分别为4345548±125822μm2,4302061±167952μm2和5016269±207934μm2;平均新生内膜面积分别为1119635±163503μm2,1135636±136555μm2和441577±74099μm2;平均最大内膜厚度分别为210±30μm,192±21μm和116±12μm。缬沙坦涂层支架组管腔面积最大,最大内膜厚度、新生内膜面积最小。AT2RmRNA在各组都有表达,在缬沙坦涂层支架组显著高于另外两组。免疫组化可见AT2R蛋白的含量在各组具有相同的趋势。结论缬沙坦洗脱支架通过上调AT2R表达,抑制血管内膜增生,可能具有防治支架术后再狭窄的作用。

Objective To study the effect of valsartan eluting-stent on vascular neointimal formation and angiotensin Ⅱ type 2 receptor （AT2R） expression and to access its feasibility to prevent in-stent restenosis and the mechanism. Methods Both the valsartan eluting-stents and the carrier eluting-stents were made with multi-layers coated methods. Bare stents, carrier eluting-stents and valsartan eluting-stents were implanted into the rabbits＇ abdominal aortias respectively. Abdominal aorta angiography was performed before and right after the operation and at 3 months after stent inplantation. The mean diameter of aortas in different groups were measured by Quantitative coronary angiography software. All the rabbits were killed 3 months after the procedure and the cross section of the stented vessel were analysed for neointimal formation. The luminal area, neointimal area, inner elastic membrane luminal area and the maximal inner-membrane thickness were compared between the 3 groups. The expressions of AT2R mRNA and the protein were determined by RT-PCR and histomorphometry. Results There were no significant differences in the mean aortic diameters among the 3 groups. The greatest luminal area and the minimal neointimal hyperplasia was found in the valsartan eluting-stents group compared with the other two groups. The mean luminal areas of the bare stents, carrier eluting stents and the valsartan eluting-stents were 4 345 548 ± 1 258 22 μm^2, 4 302 061 ± 167 952 μm^2 and 5 016 269 ± 207 934μm^2 ; the mean neointimal areas were 1 119 635 ± 163 503μm^2, 1 135 636 ± 136 555 μm^2 and 441 577 ±74 099 μm^2 and the mean maximal inner-membrane thickness were 210 ± 30 μm^2, 192 ± 21 μm^2 and 116 ± 12μm^2 respectively. The level of AT2R mRNA expression in the valsartan eluting-stents group was higher than that in the other two groups. The transcription of AT2R protein showed similar trend. Conclusion Valsartan eluting-stents enhanced AT2R mRNA and protein expression and inhibited neointimal hyperplasia which might play an important role in preventing restenosis.