Polydatin protects cardiac function against burn injury by inhibiting sarcoplasmic reticulum Ca2+ leak by reducing oxidative modification of ryanodine receptors
Polydatin protects cardiac function against burn injury by inhibiting sarcoplasmic reticulum Ca2+ leak by reducing oxidative modification of ryanodine receptors
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虎杖甙通过减少兰尼碱受体的氧化修饰，抑制肌浆网 Ca2 渗漏，从而保护心脏功能免受烧伤
DOI：
10.1016/j.freeradbiomed.2013.02.030
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发表时间：
2013-07-01
影响因子：
7.4
通讯作者：
Liu, Jie
中科院分区：
文献类型：
--
作者：
Jiang, Xin;Liu, Wenjuan;Liu, Jie
近年来的研究表明，烧伤后由于Ryanodine受体（RyR）功能异常，导致心肌肌浆网（SR）渗漏。SR Ca ~（2+）漏出导致SR Ca ~（2+）含量的部分耗竭和细胞内Ca ~（2+）稳态的紊乱，导致烧伤引起的心功能障碍的发病机制。本研究旨在探讨白藜芦醇苷在预防SR渗漏中的作用及其对烧伤引起的心功能障碍的治疗作用。我们发现，虎杖苷治疗改善心脏功能受损的烧伤30%的总体表面积。并行的心脏功能的改变，虎杖苷显着增加有缺陷的收缩期Ca 2+瞬变和收缩力烧伤创伤心肌细胞。烧伤可增加Ca ~（2+）火花的发生。钙火花介导的SR漏的增强导致烧伤损伤心肌细胞SR钙含量的部分耗竭。此外，我们发现，由RyR 2的单溴异丙烷荧光测定的心肌细胞中RyR 2中的游离巯基（还原半胱氨酸的数量）的含量在烧伤创伤的心脏中显著降低。白藜芦醇苷治疗降低细胞内活性氧水平，恢复烧伤RyR 2中游离巯基的量。同时，虎杖苷纠正钙火花介导的SR泄漏和恢复SR钙负荷。虎杖苷能显著增加收缩期Ca 2+瞬变和细胞收缩力。综上所述，本研究结果提供了第一个证据，证明虎杖苷通过降低烧伤创伤心脏RyR 2中的氧化应激来防止增强的Ca 2+火花介导的SR泄漏，从而保护心脏功能免受烧伤损伤。(C)2013 Elsevier Inc. All rights reserved.
Our recent studies demonstrate that burn trauma induces leaky sarcoplasmic reticulum (SR) in heart due to excessively active ryanodine receptor (RyR) function. SR Ca2+ leak causes partial depletion of SR Ca2+ content and disturbances in intracellular Ca2+ homeostasis, resulting in the pathogenesis of burn-generated cardiac dysfunction. This study investigated the role of polydatin, a resveratrol glucoside, in preventing SR leak and its therapeutic effect against burn-generated cardiac dysfunction. We found that polydatin treatment improved cardiac function impaired by burn injury of 30% of total body surface area. Parallel to the alterations in cardiac function, polydatin significantly increased the defective systolic Ca2+ transient and contractility in burn-traumatized cardiomyocytes. Burn injury increased the occurrence of Ca2+ sparks. The enhancement of Ca2+ spark-mediated SR leak caused partial depletion of SR Ca2+ content in burn-traumatized cardiomyocytes. Furthermore, we found that the content of free thiols (the number of reduced cysteines) in RyR2 in cardiomyocytes determined by the monobromobimane fluorescence of RyR2 was decreased markedly in burn-traumatized hearts. Polydatin treatment decreased intracellular reactive oxygen species levels and restored the amount of free thiols in RyR2 in burns. Concomitantly, polydatin corrected Ca2+ spark-mediated SR leak and restored SR Ca2+ load. The systolic Ca2+ transient and cellular contractility were significantly increased by polydatin treatment. Taken together, the present findings provide the first evidence demonstrating that polydatin prevents enhanced Ca2+ spark-mediated SR leak by reducing oxidative stress in RyR2 in burn-traumatized heart, leading to protection of cardiac function against burn injury. (C) 2013 Elsevier Inc. All rights reserved.