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胆固醇喂养兔球囊血管成形术和支架植入术后新生内膜增生中不同的炎症反应和氧化应激

Different inflammatory response and oxidative stress in neointimal hyperplasia after balloon angioplasty and stent implantation in cholesterol-fed rabbits.

作者信息

Kawamoto Riichirou, Yamashita Atsushi, Nishihira Kensaku, Furukoji Eiji, Hatakeyama Kinta, Ishikawa Tetsunori, Imamura Takuroh, Itabe Hiroyuki, Eto Tanenao, Asada Yujiro

机构信息

First Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 Japan.

出版信息

Pathol Res Pract. 2006;202(6):447-56. doi: 10.1016/j.prp.2005.12.011. Epub 2006 Apr 25.

Abstract

Inflammatory responses appear to play an important role in the occurrence of restenosis following coronary intervention. However, the contribution of C-reactive protein (CRP) and oxidative stress to restenosis after balloon angioplasty and stent implantation remains unclear. The aim of this study was to examine this issue using hyperlipidemic rabbits. Rabbits were divided into two groups; they were fed with a 0.5% cholesterol diet and with a mixed 0.5% cholesterol and 0.5% probucol diet. Each group of rabbits underwent balloon injury and stent implantation in right and left iliac arteries, respectively. Eight weeks after the intervention, we examined luminal stenosis, neointimal hyperplasia, immunoreactivity for macrophage, CRP and oxidized phosphatidylcholine (oxPC), and also the expression of CRP mRNA. The degrees of neointimal hyperplasia and immunopositive areas (%) for macrophage, CRP, and oxPC in the neointima were significantly higher after stent implantation than after balloon injury, but CRP mRNA was undetectable in either artery. Anti-oxidant probucol reduced angiographic stenosis, neointimal hyperplasia, and macrophage- and oxPC-positive areas much more significantly after stenting. The results demonstrate that the inflammatory response to the development of neointimal hyperplasia differs after balloon injury and stent implantation and that CRP deposition and oxidative stress might be involved more significantly in neointimal development after stent implantation.

摘要

炎症反应似乎在冠状动脉介入术后再狭窄的发生中起重要作用。然而,C反应蛋白(CRP)和氧化应激对球囊血管成形术和支架植入术后再狭窄的作用仍不清楚。本研究的目的是使用高脂血症兔来研究这个问题。将兔分为两组;分别用0.5%胆固醇饮食和0.5%胆固醇与0.5%普罗布考混合饮食喂养。每组兔分别在左右髂动脉进行球囊损伤和支架植入。干预8周后,我们检测了管腔狭窄、新生内膜增生、巨噬细胞、CRP和氧化磷脂酰胆碱(oxPC)的免疫反应性,以及CRP mRNA的表达。支架植入后新生内膜增生程度以及新生内膜中巨噬细胞、CRP和oxPC的免疫阳性面积(%)显著高于球囊损伤后,但在任一动脉中均未检测到CRP mRNA。抗氧化剂普罗布考在支架植入后更显著地降低了血管造影狭窄、新生内膜增生以及巨噬细胞和oxPC阳性面积。结果表明,球囊损伤和支架植入后对新生内膜增生发展的炎症反应不同,并且CRP沉积和氧化应激可能在支架植入后的新生内膜发展中更显著地起作用。

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