唑来膦酸对新生内膜增生的影响：兔颈动脉吻合模型

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model.

作者信息

Güzeloğlu Mehmet, Gül Mehmet, Reel Buket, Yürekli Ismail, Aykut Koray, Hazan Eyüp

机构信息

Department of Cardiovascular Surgery, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey.

出版信息

Anadolu Kardiyol Derg. 2011 Mar;11(2):93-100. doi: 10.5152/akd.2011.026. Epub 2011 Feb 2.

DOI:10.5152/akd.2011.026

PMID:21285021

Abstract

OBJECTIVE

The aim of the present study was to investigate the effect of zoledronic acid (ZA), as a matrix metalloproteinase inhibitor, on neointimal hyperplasia in rabbit carotid anastomosis model.

METHODS

New Zealand male rabbits were divided into two groups as placebo and treatment groups in this experimental study. After anesthesia, the right carotid artery of each rabbit was end-to-end anastomosed with an 8/0 polypropylene suture. Left carotid artery was kept as control without any operation. Placebo group (n=6) received phosphate buffered saline (PBS) (0.5mL/kg/day/s.c.) for 28 days postoperatively, whereas ZA group (n=6) received ZA (100 µg/kg/day/s.c.) for the same period. After sacrification, the anastomosed and control arteries were isolated. Morphometric and immunohistochemical examinations were performed. Statistical analyses of morphometric and immunohistochemical data were performed using two-way ANOVA and Chi-square test respectively.

RESULTS

In PBS group, vascular injury in the anastomosed artery significantly increased the intimal area (anastomosed: 112.51±61.18 µm(2)*1000 vs. control: 22.62±4.26 µm(2)*1000, p<0.01) and intima/media index (anastomosed: 0.347±0.29 vs. control: 0.075±0.01, p<0.05) compared to control artery. ZA significantly reduced the intimal area (39.29±18.21 µm(2)*1000 , p<0.01) and intima/media index (0.112±0.07, p<0.05) compared to PBS group. Additionally, α-smooth muscle actin immunopositivity was found significantly decreased in anastomosed arteries from ZA group (ZA: 2.33±0.52 vs. PBS: 3.50±0.5, p<0.05). Moreover, intensive gelatinase (MMP-2 and MMP-9) immunoreactivities were clearly seen in anastomosed arteries compared to control arteries from PBS group. ZA apparently decreased immunopositivities for gelatinases in anastomosed arteries.

CONCLUSION

ZA might be a promising agent for prevention of neointimal hyperplasia, which is the most significant cause of graft failures in late postoperative period.

摘要

目的

本研究旨在探讨作为基质金属蛋白酶抑制剂的唑来膦酸（ZA）对兔颈动脉吻合模型中新生内膜增生的影响。

方法

在本实验研究中，将新西兰雄性兔分为安慰剂组和治疗组。麻醉后，用8/0聚丙烯缝线将每只兔的右颈动脉进行端端吻合。左颈动脉作为对照，不进行任何手术。安慰剂组（n = 6）术后28天皮下注射磷酸盐缓冲盐水（PBS）（0.5mL/kg/天），而ZA组（n = 6）在同一时期皮下注射ZA（100µg/kg/天）。处死后，分离吻合动脉和对照动脉。进行形态计量学和免疫组织化学检查。分别使用双向方差分析和卡方检验对形态计量学和免疫组织化学数据进行统计分析。

结果

在PBS组中，与对照动脉相比，吻合动脉中的血管损伤显著增加了内膜面积（吻合：112.51±61.18µm²×1000 vs.对照：22.62±4.26µm²×1000，p<0.01）和内膜/中膜指数（吻合：0.347±0.29 vs.对照：0.075±0.01，p<0.05）。与PBS组相比，ZA显著降低了内膜面积（39.29±18.21µm²×1000，p<0.01）和内膜/中膜指数（0.112±0.07，p<0.05）。此外，在ZA组的吻合动脉中发现α-平滑肌肌动蛋白免疫阳性显著降低（ZA：2.33±0.52 vs.PBS：3.50±0.5，p<0.05）。此外，与PBS组的对照动脉相比，在吻合动脉中明显可见强烈的明胶酶（MMP - 2和MMP - 9）免疫反应性。ZA明显降低了吻合动脉中明胶酶的免疫阳性。