Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study.
Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study.
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甲氨蝶呤对支架内新动脉粥样硬化兔模型的影响：光学相干断层扫描研究
DOI：
10.1038/srep33657
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发表时间：
2016-09-20
影响因子：
4.6
通讯作者：
Hou J
中科院分区：
文献类型：
--
作者：
Zhang R;Chen S;Zhang H;Liu Q;Xing J;Zhao Q;Wang Y;Yu B;Hou J
本研究采用光学相干断层扫描(OCT)技术，研究了全身性甲氨蝶呤联合药物洗脱支架对支架内新生动脉硬化的影响。将西罗莫司洗脱支架植入200只雄性新西兰白兔的右侧颈总动脉；动物在支架植入前一周开始接受高脂饮食。每只动物被随机分配到4组中的1组，每周接受4或12周的静脉注射甲氨蝶呤(0.4 mg/kg)或安慰剂。支架置入后4周或12周取材，进行OCT和组织学分析。在采集动脉节段之前，采集血液以测定细胞因子水平。与对照组相比，接受甲氨蝶呤治疗的动物表现出较低的富脂内膜和每支低信号强度层、较小的新生内膜面积和较小的新生内膜厚度；在接受甲氨蝶呤治疗的动物中也可以看到较大的纤维帽厚度和较小的管腔面积。甲氨蝶呤治疗组大鼠血清白介素2、黏附分子和核因子-κBp65水平降低，IL-10水平升高。以促炎通路为靶点可能是预防再狭窄的有效方法，而不存在晚期血栓形成的长期风险。
This study used optical coherence tomography (OCT) to investigate the effects of systemic methotrexate, in combination with a drug-eluting stent, on in-stent neoatherosclerosis in a rabbit model. Sirolimus-eluting stents were surgically implanted in the right common carotid arteries of 200 male New Zealand White rabbits; the animals received a high-fat diet, beginning one week before stent implantation. Each animal was randomly assigned to 1 of 4 groups, receiving intravenous injections of either methotrexate (0.4 mg/kg) or placebo weekly for 4 or 12 weeks. Stented arterial segments were harvested after stenting for 4 or 12 weeks, and processed for OCT and histological analysis. Prior to harvesting the arterial segments, blood was collected for the determinations of cytokine levels. Compared with the control animals, the methotrexate-treated animals showed lower rates of lipid-rich intima and per-strut low-signal intensity layers, smaller neointimal areas, and reduced neointimal thickness; larger fibrous cap thicknesses and smaller lumen areas were also seen in the animals receiving methotrexate. The levels of serum interleukin, adhesion molecules, and nuclear factor-κB p65 decreased and IL-10 level increased in the methotrexate-treated animals. Targeting the pro-inflammatory pathways may be an effective way to prevent restenosis without the long-term risk of late thrombosis.
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影响因子：
27.4
作者：
Conaghan PG;Østergaard M;Bowes MA;Wu C;Fuerst T;van der Heijde D;Irazoque-Palazuelos F;Soto-Raices O;Hrycaj P;Xie Z;Zhang R;Wyman BT;Bradley JD;Soma K;Wilkinson B
通讯作者：
Wilkinson B
影响因子：
27.4
作者：
Haagsma, CJ;Blom, HJ;van de Putte, LBA
通讯作者：
van de Putte, LBA
影响因子：
24
作者：
Takano, Masamichi;Yamamoto, Masanori;Mizuno, Kyoichi
通讯作者：
Mizuno, Kyoichi
影响因子：
5.7
作者：
Hou, Jingbo;Qi, Hai;Jang, Ik-Kyung
通讯作者：
Jang, Ik-Kyung
影响因子：
5.7
作者：
Tian, Jinwei;Hou, Jingbo;Jang, Ik-Kyung
通讯作者：
Jang, Ik-Kyung