Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation
Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation
复制标题
萝卜硫素预防糖尿病心肌病与 Nrf2 表达和转录激活上调有关
DOI：
10.1016/j.yjmcc.2013.01.008
复制
发表时间：
2013-04-01
影响因子：
5
通讯作者：
Cai, Lu
中科院分区：
文献类型：
--
作者：
Bai, Yang;Cui, Wenpeng;Cai, Lu
本研究旨在探讨萝卜硫素（SFN）是否可以预防糖尿病心肌病。通过多次腹腔注射低剂量链脲佐菌素在 FVB 小鼠中诱导 1 型糖尿病。高血糖和年龄匹配的对照小鼠接受或不接受 SFN 治疗，每周 5 天，每天 0.5 mg/kg，持续 3 个月，然后保持至 6 个月。在患糖尿病 3 个月和 6 个月时，评估血压和心脏功能。通过蛋白质印迹、实时 qPCR 和组织病理学检查评估心脏纤维化、炎症和氧化损伤。 SFN在3个月和6个月时均显着预防糖尿病引起的高血压和心功能不全，还可以预防糖尿病引起的心脏肥大（增加心脏重量与胫骨长度的比率以及心房钠尿肽mRNA和蛋白质的表达）和纤维化（增加胶原蛋白的积累以及结缔组织生长因子和组织生长因子-β的表达）。 SFN 还几乎完全预防糖尿病引起的心脏氧化损伤（3-硝基酪氨酸和 4-羟基壬烯醛的积累增加）和炎症（肿瘤坏死因子-α 和纤溶酶原激活剂抑制剂 1 表达增加）。 SFN 上调 NFE2 相关因子 2 (Nrf2) 的表达和转录活性，这反映在 Nrf2 核积累和磷酸化以及 Nrf2 下游抗氧化剂的 mRNA 和蛋白表达增加上。此外，在培养的 H9c2 心脏细胞中，用 siRNA 沉默 Nrf2 基因可以消除 SFN 对高葡萄糖诱导的纤维化反应的预防作用。这些结果表明SFN可以预防糖尿病引起的心肌病，这与上调Nrf2表达和转录功能有关。 (C) 2013 Elsevier Ltd. 保留所有权利。
This study was to investigate whether sulforaphane (SFN) can prevent diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by multiple intraperitoneal injections with low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. At 3 and 6 months of diabetes, blood pressure and cardiac function were assessed. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot, real-time qPCR, and histopathological examination. SFN significantly prevented diabetes-induced high blood pressure and cardiac dysfunction at both 3 and 6 months, and also prevented diabetes-induced cardiac hypertrophy (increased the ratio of heart weight to tibia length and the expression of atrial natriuretic peptide mRNA and protein) and fibrosis (increased the accumulation of collagen and expression of connective tissue growth factor and tissue growth factor-beta). SFN also almost completely prevented diabetes-induced cardiac oxidative damage (increased accumulation of 3-nitrotyrosine and 4-hydroxynonenal) and inflammation (increased tumor necrotic factor-alpha and plasminogen activator inhibitor 1 expression). SFN up-regulated NFE2-related factor 2 (Nrf2) expression and transcription activity that was reflected by increased Nrf2 nuclear accumulation and phosphorylation as well as the mRNA and protein expression of Nrf2 downstream antioxidants. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the SFN's prevention of high glucose-induced fibrotic response. These results suggest that diabetes-induced cardiomyopathy can be prevented by SFN, which was associated with the up-regulated Nrf2 expression and transcription function. (C) 2013 Elsevier Ltd. All rights reserved.