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番茄红素通过调节NO/cGMP途径和Rho相关激酶表达改善血管同种异体移植中的移植动脉硬化。

Lycopene Ameliorates Transplant Arteriosclerosis in Vascular Allograft Transplantation by Regulating the NO/cGMP Pathways and Rho-Associated Kinases Expression.

作者信息

He Yunqiang, Xia Peng, Jin Hao, Zhang Yan, Chen Bicheng, Xu Ziqiang

机构信息

Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.

Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.

出版信息

Oxid Med Cell Longev. 2016;2016:3128280. doi: 10.1155/2016/3128280. Epub 2016 Dec 5.

Abstract

Transplant arteriosclerosis is considered one of the major factors affecting the survival time of grafts after organ transplantation. In this study, we proposed a hypothesis of whether lycopene can protect grafted vessels through regulating key proteins expression involved in arteriosclerosis. Allogeneic aortic transplantation was performed using Brow-Norway rats as donors and Lewis rats as recipients. After transplantation, the recipients were divided into two groups: the allograft group and the lycopene group. Negative control rats (isograft group) were also established. Histopathological staining was performed to observe the pathological changes, and the expression levels of Ki-67, caspase-3, Rho-associated kinases, intercellular adhesion molecules (ICAM-1), and eNOS were assessed. Western blotting analysis and real-time PCR were also performed for quantitative analysis. The histopathological staining showed that vascular stenosis and intimal thickening were not evident after lycopene treatment. The Ki-67, ROCK1, ROCK2, and ICAM-1 expression levels were significantly decreased. However, eNOS expression in grafted arteries and plasma cGMP concentration were increased after lycopene treatment. Lycopene could alleviate vascular arteriosclerosis in allograft transplantation via downregulating Rho-associated kinases and regulating key factor expression through the NO/cGMP pathways, which may provide a potentially effective method for transplant arteriosclerosis in clinical organ transplantation.

摘要

移植动脉硬化被认为是影响器官移植后移植物存活时间的主要因素之一。在本研究中,我们提出了一个假设,即番茄红素是否可以通过调节参与动脉硬化的关键蛋白表达来保护移植血管。采用布朗-挪威大鼠作为供体、刘易斯大鼠作为受体进行同种异体主动脉移植。移植后,将受体分为两组:同种异体移植组和番茄红素组。还建立了阴性对照大鼠(同基因移植组)。进行组织病理学染色以观察病理变化,并评估Ki-67、半胱天冬酶-3、Rho相关激酶、细胞间黏附分子(ICAM-1)和内皮型一氧化氮合酶(eNOS)的表达水平。还进行了蛋白质免疫印迹分析和实时定量PCR进行定量分析。组织病理学染色显示,番茄红素处理后血管狭窄和内膜增厚不明显。Ki-67、ROCK1、ROCK2和ICAM-1的表达水平显著降低。然而,番茄红素处理后移植动脉中的eNOS表达和血浆cGMP浓度升高。番茄红素可通过下调Rho相关激酶并通过NO/cGMP途径调节关键因子表达来减轻同种异体移植中的血管动脉硬化,这可能为临床器官移植中的移植动脉硬化提供一种潜在的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88e2/5165158/a14acf47af07/OMCL2016-3128280.001.jpg

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