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自发性高血压大鼠颈总动脉早期硬化改变中LOX-1和MCP-1的表达上调与病变严重程度相关

Severity dependent up-regulations of LOX-1 and MCP-1 in early sclerotic changes of common carotid arteries in spontaneously hypertensive rats.

作者信息

Hamakawa Y, Omori N, Ouchida M, Nagase M, Sato K, Nagano I, Shoji M, Fujita T, Abe K

机构信息

Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Japan.

出版信息

Neurol Res. 2004 Oct;26(7):767-73. doi: 10.1179/016164104225016074.

Abstract

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) and monocyte chemoattractant protein-1 (MCP-1) are molecules involving in the initiation and progression of atherosclerosis. In order to examine a possible difference in LOX-1 and MCP-1 expressions depending on the severity of early stage of atherosclerosis, we investigated atherosclerotic changes by exposure to hypertension and hyperlipidemia in common carotid arteries (CCAs) of stroke-prone spontaneously hypertensive rat (SHR-SP). Three rat model groups such as control [Wistar Kyoto rat (WKY) group], hypertension (SHR-SP group) and hypertension + hyperlipidemia [SHR-SP + high fat and cholesterol (HFC) group] were used. Body weights, brain weights, systolic blood pressures and serum levels of total cholesterol, low-density lipoprotein and triglyceride were measured at 0, 5, 10 and 15 days after appropriate diet. Immunohistochemistry showed that the positive area and the strength of LOX-1 and MCP-1 were larger in the SHR-SP + HFC group than in the SHR-SP group, while no immunoreactivities were found in the WKY group. Conventional RT-PCR and real-time PCR analyses showed that mRNAs of those in the SHR-SP group were higher with greater up-regulation in the SHR-SP + HFC group. LOX-1 and MCP-1 expressions were coordinately up-regulated at mRNA and protein levels in an early stage of sclerosis depending on the severity of atherosclerotic stress. Activations of LOX-1 and MCP-1 are collectively involved in the early stage of atherosclerosis.

摘要

凝集素样氧化低密度脂蛋白受体(LOX-1)和单核细胞趋化蛋白-1(MCP-1)是参与动脉粥样硬化发生和发展的分子。为了研究LOX-1和MCP-1表达是否因动脉粥样硬化早期严重程度的不同而存在差异,我们通过使易卒中型自发性高血压大鼠(SHR-SP)的颈总动脉(CCA)暴露于高血压和高脂血症来研究动脉粥样硬化的变化。使用了三个大鼠模型组,即对照组[Wistar Kyoto大鼠(WKY)组]、高血压组(SHR-SP组)和高血压+高脂血症组[SHR-SP+高脂肪和胆固醇(HFC)组]。在给予适当饮食后的0、5、10和15天测量体重、脑重、收缩压以及总胆固醇、低密度脂蛋白和甘油三酯的血清水平。免疫组织化学显示,SHR-SP+HFC组中LOX-1和MCP-1的阳性面积和强度大于SHR-SP组,而WKY组未发现免疫反应性。传统RT-PCR和实时PCR分析表明,SHR-SP组中这些分子的mRNA水平较高,在SHR-SP+HFC组中上调幅度更大。根据动脉粥样硬化应激的严重程度,在硬化早期,LOX-1和MCP-1的表达在mRNA和蛋白质水平上协同上调。LOX-1和MCP-1的激活共同参与动脉粥样硬化的早期阶段。

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