Bailcalin Protects against Diabetic Cardiomyopathy throu Keap1/Nrf2/AMPK-Mediated Antioxidative and Lipid-Lowering Effects
Bailcalin Protects against Diabetic Cardiomyopathy throu Keap1/Nrf2/AMPK-Mediated Antioxidative and Lipid-Lowering Effects
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Bailcalin 通过 Keap1/Nrf2/AMPK 介导的抗氧化和降脂作用预防糖尿病心肌病。
DOI：
10.1155/2019/3206542
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发表时间：
2019-07-01
影响因子：
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通讯作者：
Qiu, Chun-guang
中科院分区：
文献类型：
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作者：
Li, Ran;Liu, Yuan;Qiu, Chun-guang
先前的研究表明，黄芩苷 (BAI) 可预防不同疾病模型下的心脏损伤。本研究调查了 BAI 是否可以预防 2 型糖尿病 (T2DM) 相关的心肌病。通过注射链脲佐菌素和高脂饮食联合小鼠建立T2DM。 BAI 每天给药，持续 6 个月。评估心脏功能后，取出小鼠心脏并进行处理以进行形态学、生化和分子机制分析。分离新生大鼠心肌细胞（NRCM）并用高葡萄糖和棕榈酸酯（HG/Pal）处理进行体外研究。 BAI 显着改善 T2DM 诱导的心肌细胞肥大、间质纤维化和脂质积累，同时显着改善糖尿病小鼠的心脏功能。从机械角度来看，BAI 恢复了 AMPK 磷酸化的降低，并增强了 Nrf2 的表达和核易位。在体外实验中，BAI 还通过增加 p-AMPK 和 Nrf2 积累，防止 NRCM 免受 HG/Pal 诱导的细胞凋亡和氧化应激损伤。 BAI恢复p-AMPK的方式似乎与NRCM中沉默AMPK或Nrf2后Nrf2的抗氧化作用有关。此外，BAI 通过抑制 Nrf2 泛素化和 Keap1 介导的降解来调节 Nrf2。这项研究表明，BAI 通过 Keap1/Nrf2/AMPK 介导的抗氧化和降脂作用，在体内和体外减轻糖尿病相关的心功能障碍和心肌细胞损伤。 BAI可能是糖尿病心肌病治疗的潜在辅助药物。
Previous studies demonstrated that Bailcalin (BAI) prevented cardiac injuries under different disease models. Whether BAI protected against type 2 diabetes mellitus- (T2DM-) associated cardiomyopathy was investigated in this study. T2DM was established by the combination of streptozotocin injection and high-fat diet in mice. BAI was administered daily for 6 months. After evaluating cardiac functions, mice hearts were removed and processed for morphological, biochemical, and molecular mechanism analyses. Neonatal rat cardiomyocytes (NRCM) were isolated and treated with high glucose and palmitate (HG/Pal) for in vitro investigation. BAI significantly ameliorated T2DM-induced cardiomyocyte hypertrophy, interstitial fibrosis, and lipid accumulation accompanied by markedly improved cardiac functions in diabetic mice. Mechanically, BAI restored decreased phosphorylation of AMPK and enhanced expression and nuclei translocation of Nrf2. In in vitro experiments, BAI also prevented NRCM from HG/Pal-induced apoptosis and oxidative stress injuries by increasing p-AMPK and Nrf2 accumulation. The means by which BAI restored p-AMPK seemed to be related to the antioxidative effects of Nrf2 after silencing AMPK or Nrf2 in NRCM. Furthermore, BAI regulated Nrf2 by inhibiting Nrf2 ubiquitination and consequent degradation mediated by Keap1. This study showed that BAI alleviated diabetes-associated cardiac dysfunction and cardiomyocyte injuries in vivo and in vitro via Keap1/Nrf2/AMPK-mediated antioxidation and lipid-lowering effects. BAI might be a potential adjuvant drug for diabetes cardiomyopathy treatment.