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首页> 外文期刊>Platelets >R-lipoic acid overdosing affects platelet life span via ROS mediated autophagy
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R-lipoic acid overdosing affects platelet life span via ROS mediated autophagy

机译：R-硫辛酸过量通过ROS介导的自噬地影响血小板寿命

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摘要

R-lipoic acid (ALA), a powerful antioxidant valuable for the treatment of diabetes and its complications, has been reported to exhibit an antiplatelet activity in vitro. The aim of this study was to investigate the effect and mechanism of ALA on platelets in vivo. Sprague-Dawley (SD) male rats were intravenously administered with low-dose ALA (20 mg/kg/d), high-dose ALA (80 mg/kg/d) and saline, respectively. Platelets count and bone marrow smear were evaluated and the expressions of markers related to apoptosis and autophagy were measured. Platelet clearance analysis was conducted out on mice. The results showed that high-dose ALA administration could significantly decrease platelet count by 43% compared with control group, whereas, megakaryocytes showed no difference in the number. Moreover, high-dose ALA administration led to significant reduction in half-life of circulating platelets, indicative of enhanced rate of platelet clearance. Interesting, high-dose ALA administration could increase the level of reactive oxygen species (ROS) in platelets and induce autophagy without affecting apoptosis. Our finding also showed that high ALA-induced autophagy in platelets was mediated by class III PtdIns3K activity, which could be reversed by 3-methyladenine (3-MA). Moreover, AKT and MAPK/ERK pathways were also observed to be involved in the regulation of autophagy in platelets. Thus, high-dose ALA could induce autophagy in platelets through modulating the activity of class III PtdIns3K, which was associated with decreased count of circulating platelets and shortened lifespan of platelets.
机译：据报道，R-硫辛酸（ALA）是一种针对糖尿病治疗糖尿病及其并发症的强大抗氧化剂，以在体外表现出抗血小板活性。本研究的目的是探讨ALA对体内血小板的影响和机制。 Sprague-Dawley（SD）静脉内大鼠分别用低剂量ALA（20mg / kg / d），高剂量ALA（80mg / kg / d）和盐水施用。评价血小板数和骨髓涂片，并测量与细胞凋亡和自噬相关的标志物的表达。在小鼠上进行血小板间隙分析。结果表明，与对照组相比，高剂量ALA给药可显着降低43％的血小板计数，而巨核细胞显示数量没有差异。此外，高剂量ALA给药导致循环血小板半衰期显着降低，指示血小板间隙的增强率。有趣的是，高剂量Ala施用可以增加血小板中的活性氧物质（ROS）的水平，并在不影响细胞凋亡的情况下诱导自噬。我们的发现还表明，血小板中的高ALA诱导的自噬由III类PTDINS3K活性介导，其可以通过3-甲基腺嘌呤（3-MA）反转。此外，还观察到AKT和MAPK / ERK途径参与血小板中自噬的调节。因此，通过调节III类PTDINS3K的活性，高剂量ALA可以通过调节III类PTDINS3K的活性，这与循环血小板的计数降低和血小板的寿命相关联。

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  • 来源
    《Platelets》 |2018年第7期|共7页
  • 作者

    Liu Jing; Song Qingqing; Huang Yanwei; Sun Wu; Lu Dingqiang; Zhou Bo;

  • 作者单位

    Nanjing Tech Univ Jiangsu Prov Inst Mat Med Sch Pharmaceut Sci Jiangsu Ctr Safety Evaluat Drugs;

    Nanjing Tech Univ Jiangsu Prov Inst Mat Med Sch Pharmaceut Sci Jiangsu Ctr Safety Evaluat Drugs;

    Nanjing Tech Univ Jiangsu Prov Inst Mat Med Sch Pharmaceut Sci Jiangsu Ctr Safety Evaluat Drugs;

    Nanjing Tech Univ Jiangsu Prov Inst Mat Med Sch Pharmaceut Sci Jiangsu Ctr Safety Evaluat Drugs;

    Nanjing Tech Univ Jiangsu Prov Inst Mat Med Sch Pharmaceut Sci Jiangsu Ctr Safety Evaluat Drugs;

    Nanjing Tech Univ Jiangsu Prov Inst Mat Med Sch Pharmaceut Sci Jiangsu Ctr Safety Evaluat Drugs;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 基础医学;
  • 关键词

    Autophagy; life span; R-lipoic acid; ROS;

    机译：自噬;寿命;r-硫辛酸;ROS;

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