Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor.
Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor.
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DOI：
10.1371/journal.pone.0069452
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Su G
中科院分区：
文献类型：
--
作者：
Hao E;Lang F;Chen Y;Zhang H;Cong X;Shen X;Su G
脓毒性心肌病是一种严重的疾病，仍然是临床管理的挑战。本研究探讨了天然多酚化合物白藜芦醇是否可以作为预防性治疗来减轻脓毒症相关的心肌损伤;通过体外和体内实验破译了潜在的分子机制。通过腹腔注射LPS建立内毒素诱导的心肌病小鼠模型，并向动物体内给予白藜芦醇。测定血清LDH和CK活性以检测心肌损伤，超声心动图监测心脏结构和功能。在心脏组织中检查各种细胞因子/趋化因子和Nrf 2抗氧化防御系统。在培养的原代人心肌细胞中进一步研究了白藜芦醇对LPS诱导的Nrf 2活化、ROS产生和凋亡性细胞死亡的影响。使用Nrf 2特异性siRNA来定义其在白藜芦醇介导的心肌细胞保护作用中的作用。白藜芦醇预处理显著减弱LPS诱导的小鼠心肌损伤，这与抑制促炎细胞因子的产生和增强心脏中Nrf 2的激活有关。在培养的原代人心肌细胞中，白藜芦醇激活Nrf 2，抑制LPS诱导的ROS产生，并有效地保护细胞免受LPS诱导的细胞凋亡。Nrf 2的敲低废除了白藜芦醇介导的对细胞免于LPS诱导的细胞死亡的保护。白藜芦醇通过涉及Nrf 2抗氧化防御途径的机制有效地减轻内毒素诱导的心脏毒性。我们的数据表明，白藜芦醇可能被开发为一个有用的预防管理脓毒性心肌病。
Septic cardiomyopathy is a severe condition that remains a challenge for clinical management. This study investigated whether the natural polyphenolic compound resveratrol could be used as a prophylactic treatment to alleviate sepsis-related myocardial injury; the underlying molecular mechanisms were deciphered by both in vitro and in vivo experiments. A mouse model of endotoxin-induced cardiomyopathy was developed by intraperitoneal injection of LPS, and resveratrol was administered prophylatically to the animals. Serum LDH and CK activities were measured to detect myocardial injury, and echocardiography was performed to monitor cardiac structure and function. Various cytokines/chemokines and the Nrf2 antioxidant defense system were examined in the heart tissue. The effects of resveratrol on LPS-induced Nrf2 activation, ROS generation, and apoptotic cell death were further investigated in cultured primary human cardiomyocytes. An Nrf2 specific siRNA was used to define its role in resveratrol-mediated cardiomyocyte protective effect. Resveratrol pretreatment significantly attenuated LPS-induced myocardial injury in mice, which was associated with suppressed proinflammatory cytokine production and enhanced Nrf2 activation in the heart. In cultured primary human cardiomyocytes, resveratrol activated Nrf2, inhibited LPS-induced ROS generation, and effectively protected the cells from LPS-induced apoptotic cell death. Knockdown of Nrf2 abrogated resveratrol-mediated protection of the cells from LPS-induced cell death. Resveratrol effectively alleviates endotoxin-induced cardiac toxicity through mechanisms that involve the Nrf2 antioxidant defense pathway. Our data suggest that resveratrol might be developed as a useful prophylactic management for septic cardiomyopathy.
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DOI：
10.1152/ajpheart.00393.2005
发表时间：
2005-11-01
影响因子：
4.8
作者：
Hall, G;Singh, IS;Rogers, TB
通讯作者：
Rogers, TB
影响因子：
--
作者：
Hotchkiss, RS;Tinsley, KW;Karl, IE
通讯作者：
Karl, IE
影响因子：
27.4
作者：
Gao Xuzhu;Komai-Koma, Mousa;Xu, Damo
通讯作者：
Xu, Damo
DOI：
10.1016/j.bbrc.2008.11.110
发表时间：
2009-01-16
影响因子：
3.1
作者：
Chen, Chun-Juan;Yu, Wei;Wang, Wei
通讯作者：
Wang, Wei
DOI：
10.2165/00129784-200202010-00001
发表时间：
2002-01-01
期刊：
American journal of cardiovascular drugs : drugs, devices, and other interventions
影响因子：
--
作者：
Chatterjee, Kanu
通讯作者：
Chatterjee, Kanu