Apoptosis, proliferation, and morphology during vein graft remodeling in rabbits.
Apoptosis, proliferation, and morphology during vein graft remodeling in rabbits.
复制标题
兔静脉移植重塑过程中的细胞凋亡、增殖和形态。
DOI：
10.4238/gmr.15048701
复制
发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Liu, J C
中科院分区：
文献类型：
--
作者：
Wang, Q;Xu, H;Wang, W J;Liu, J C
新内膜的形成和动脉粥样硬化限制了长期使用静脉移植物重建缺血组织。近年来，研究证实增殖细胞核抗原（PCNA）在细胞增殖中起着重要作用。我们的研究证实，在静脉移植后28天，PCNA表达明显增加。我们使用兔而不是啮齿动物作为更有代表性的人静脉移植模型，目的是利用形态计量学和免疫组织化学分析、western blot、末端脱氧核苷酸转移酶dUTP刻痕末端标记和透射电子显微镜（TEM）来建立细胞增殖和凋亡的时间变化过程。将42只健康纯种雄性新西兰大白兔颈外静脉移植到颈总动脉上。将家兔分为7组，分别于术前、术后1、3、7、14、28、90天采集静脉移植物。随后检查狭窄和凋亡程度，PCNA蛋白水平和TEM形态学。术后第1天内膜厚度略有下降，但随后持续增加至第90天。Western blot和免疫组化均显示第1天PCNA表达降低，但随后水平升高，在术后7天达到峰值。术后第7天细胞凋亡最低，此后一直维持在较低水平。随着移植物再狭窄的进展，透射电镜显示了细胞凋亡的迹象。移植后细胞增殖和细胞凋亡同时发生，表明这两个过程都参与了移植物的重塑。细胞凋亡水平在术后第1天至第3天最高，而增殖在第7天达到顶峰。
Neo-intima development and atherosclerosis limit the long-term use of vein grafts for revascularization of ischemic tissues. Recently, studies have confirmed that proliferating cell nuclear antigen (PCNA) plays an important role in cell proliferation. Our research confirmed that 28 days after vein transplantation, PCNA expression increases significantly. Using rabbits, rather than rodents, for a more representative model of human vein grafts, we aimed to establish a time course of changes in cell proliferation and apoptosis using morphometric and immunohistochemical analyses, western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling, and transmission electron microscopy (TEM). The external jugular veins of 42 healthy purebred male New Zealand white rabbits were grafted onto their common carotid arteries. The rabbits were divided into seven groups, with vein grafts being harvested before surgery, and at 1, 3, 7, 14, 28, and 90 days afterwards. The extent of stenosis and apoptosis, PCNA protein levels, and TEM morphology were subsequently examined. Intimal thickness was slightly decreased 1 day following surgery, but then increased continuously until the 90th day. Western blot and immunohistochemistry both indicated lowered PCNA expression on day 1, although levels subsequently increased, peaking at 7 days post-surgery. After surgery, apoptosis was lowest on day 7, and remained low thereafter. TEM revealed signs of apoptosis as vein graft restenosis progressed. Proliferation and apoptosis co-occurred following grafting, indicating that both processes were involved in vein graft remodeling. Apoptosis levels were highest between days 1 and 3 after surgery, whereas proliferation culminated on the 7th day.