...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular and Cellular Cardiology >Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway
【24h】

Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway

机译：萝卜硫素可能通过逆转氧化应激对LKB1 / AMPK通路的抑制作用来预防2型糖尿病小鼠的心肌病发展

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Type 2 diabetes mellitus (T2DM)-induced cardiomyopathy is associated with cardiac oxidative stress, inflammation, and remodeling. Sulforaphane (SFN), an isothiocyanate naturally presenting in widely consumed vegetables, particularly broccoli, plays an important role in cardiac protection from diabetes. We investigated the effect of SFN on T2DM-induced cardiac lipid accumulation and subsequent cardiomyopathy. Male C57BL/6J mice were fed a high-fat diet for 3 months to induce insulin resistance, followed by a treatment with 100 mg/kg body-weight streptozotocin to induce hyperglycemia; we referred to it as the T2DM mouse model. Other age-matched mice were fed a normal diet as control. T2DM and control mice were treated with or without 4-month SFN at 0.5 mg/kg daily five days a week. At the study's end, cardiac function was assessed. SFN treatment significantly attenuated cardiac remodeling and dysfunction induced by T2DM. SFN treatment also significantly inhibited cardiac lipid accumulation, measured by Oil Red O staining, and improved cardiac inflammation oxidative stress and fibrosis, shown by down-regulating diabetes-induced PAI-1, TNF-alpha, CTGF, TGF-beta, 3-NT, and 4-HNE expression. Elevated 4-HNE resulted in the increase of 4-HNE-LKB1 adducts that should inhibit LKB1 and subsequent AMPK activity. SFN upregulated the expression of Nrf2 and its downstream genes, NQO1 and HO-1, decreased 4-HNE-LKB1 adducts and then reversed diabetes-induced inhibition of LKB1/AMPK and its downstream targets, including sirtuin 1, PGC-1 alpha, phosphorylated acetyl-CoA carboxylase, carnitine palmitoyl transferase-1, ULK1, and light chain-3 II. These results suggest that SFN treatment to T2DM mice may attenuate the cardiac oxidative stress-induced inhibition of LKB1/AMPK signaling pathway, thereby preventing T2D-Minduced lipotoxicity and cardiomyopathy. (C) 2014 Elsevier Ltd. All rights reserved.
机译：2型糖尿病（T2DM）诱发的心肌病与心脏氧化应激，炎症和重塑有关。萝卜硫素（SFN）是一种天然存在于被广泛食用的蔬菜（尤其是西兰花）中的异硫氰酸盐，在保护心脏免受糖尿病的侵害中起着重要的作用。我们调查了SFN对T2DM诱导的心脏脂质蓄积和随后的心肌病的影响。给雄性C57BL / 6J小鼠喂食高脂饮食3个月以诱导胰岛素抵抗，然后以100 mg / kg体重的链脲佐菌素治疗以诱导高血糖。我们将其称为T2DM鼠标模型。给其他年龄相匹配的小鼠喂食正常饮食作为对照。将T2DM和对照小鼠每天或每星期5天每天以0.5 mg / kg的剂量使用4个月的SFN进行治疗或不进行治疗。在研究结束时，评估了心脏功能。 SFN治疗可显着减轻T2DM引起的心脏重塑和功能障碍。 SFN治疗还可以通过油红O染色显着抑制心脏脂质积聚，并通过下调糖尿病诱导的PAI-1，TNF-α，CTGF，TGF-β，3-NT表现出改善的心脏炎症氧化应激和纤维化。和4-HNE表达。升高的4-HNE导致应抑制LKB1和随后AMPK活性的4-HNE-LKB1加合物增加。 SFN上调Nrf2及其下游基因NQO1和HO-1的表达，降低4-HNE-LKB1加合物，然后逆转糖尿病引起的对LKB1 / AMPK及其下游靶标的抑制，包括沉默调节蛋白1，PGC-1 alpha，磷酸化乙酰辅酶A羧化酶，肉碱棕榈酰转移酶1，ULK1和轻链3 II。这些结果表明，SFN对T2DM小鼠的治疗可能会减弱心脏氧化应激诱导的LKB1 / AMPK信号通路的抑制，从而预防T2D-M诱导的脂毒性和心肌病。 （C）2014 Elsevier Ltd.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号