Evidence of increased oxidative stress in aged mesenteric lymphatic vessels.
Evidence of increased oxidative stress in aged mesenteric lymphatic vessels.
复制标题
老化肠系膜淋巴管氧化应激增加的证据。
DOI：
10.1089/lrb.2011.0022
复制
发表时间：
2012
影响因子：
1.4
通讯作者：
Gashev,AnatoliyA
中科院分区：
文献类型：
--
作者：
Thangaswamy,Sangeetha;Bridenbaugh,EricA;Gashev,AnatoliyA
背景：我们先前已经表明，衰老与大鼠肠系膜淋巴管（MLV）收缩力减弱有关。然而，导致这种衰老相关的收缩性变性的具体机制仍然未知。衰老通常与氧化应激的升高有关，并且活性氧（ROS）已被证明会降低MLV的收缩性。因此，在本研究中，我们试图评估衰老是否与MLV中氧化应激和氧化损伤水平的增加有关。方法和结果：从9月龄和24月龄Fischer-344大鼠中分离MLV，并进行以下实验技术：测量总超氧化物歧化酶（SOD）活性;通过测量硫代巴比妥酸反应物质（TBARS）估计脂质过氧化水平;检测活MLV中的超氧化物和线粒体ROS; Western印迹分析，以及SOD亚型和硝基酪氨酸蛋白的免疫组织化学标记。我们发现，衰老与细胞超氧化物和线粒体ROS水平的增加，同时减少Cu/Zn-SOD蛋白表达和总SOD酶活性在MLV。这种氧化应激的增加和抗氧化活性的降低与增加脂质（如TBARS所示）和蛋白质（如硝基酪氨酸标记所示）氧化损伤的证据相关：因此，我们首次证明，衰老相关的氧化应激和氧化损伤的增加确实存在于MLV的壁，并可能有助于我们以前报道的衰老相关的淋巴泵功能障碍。
Background:We have previously shown that aging is associated with weakened rat mesenteric lymphatic vessel (MLV) contractility. However, the specific mechanisms contributing to this aging-associated contractile degeneration remain unknown. Aging is often associated with elevations in oxidative stress, and reactive oxygen species (ROS) have been shown to reduce the contractility of MLV. Thus in the present study, we sought to assess whether aging is associated with increased levels of oxidative stress and oxidative damage in MLV.Methods and Results:MLV were isolated from 9-mo- and 24-mo-old Fischer-344 rats and subjected to the following experimental techniques: measurement of total superoxide dismutase (SOD) activity; estimation of lipid peroxidation levels via measurement of thiobarbituric acid reactive substances (TBARS); detection of superoxide and mitochondrial ROS in live MLV; Western blot analysis, and immunohistochemical labeling of the SOD isoforms and nitro-tyrosine proteins. We found that aging is associated with increased levels of cellular superoxide and mitochondrial ROS concomitant with a reduction in Cu/Zn-SOD protein expression and total SOD enzymatic activity in MLV. This increase in oxidative stress and decrease in antioxidant activity was associated with evidence of increased lipid (as indicated by TBARS) and protein (as indicated by nitro-tyrosine labeling) oxidative damage.Conclusions:Thus for the first time, we demonstrate that aging-associated increases in oxidative stress and oxidative damage is indeed present in the walls of MLV and may contribute to the aging-associated lymphatic pump dysfunction we previously reported.