通过抑制RAGE-依赖性炎症,THBru可以减轻糖尿病心肌病
Heng-Hui Xu1,2,3, Sheng-Xin Hao1,2,3, He-Yang Sun1,2,3
1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy, and Department of Cardiology, the Second Affiliated Hospital, Harbin Medical University, Harbin, 150000, China.
Acta pharmacologica Sinica
|June 11, 2024
概括
甲基柏鲁宾 (THBru) 通过抑制先进的糖化最终产品 (RAGE) 的受体,防止糖尿病心肌病 (DCM). 这种作用减少了炎症和氧化应激,改善了糖尿病小鼠的心脏功能.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 糖尿病心肌病 (DCM) 是糖尿病的一个严重并发症,导致心力衰竭和心脏重塑.
- 水 (THBru) 已显示出逆转心脏衰老和预防腹膜粘附的潜力.
- THBru对DCM的保护机制在很大程度上仍未被探索.
研究的目的:
- 在小鼠模型中研究THBru对DCM的保护作用.
- 阐明THBru在DCM中的作用的潜在分子机制.
主要方法:
- 将THBru给db/db小鼠,并通过心声学评估心脏功能.
- 在体外研究中,使用暴露于高葡萄糖 (HG) 的新生小鼠心肌细胞 (NMCMs).
- 分子对接,表面等离子体共振 (SPR) 和DARTS分析以确定THBru的目标及其对PI3K/AKT/NF-κB通路的影响.
主要成果:
- 在db/db小鼠中,THBru显著改善了心脏缩和透析功能,并减弱了心脏重塑.
- THBru改善了HG诱导的心肌细胞损伤,增大,炎症和反应性氧物种 (ROS) 生产.
- THBru直接与RAGE结合,导致PI3K/AKT/NF-κB通路的失活,这种情况因RAGE过度表达而逆转.
结论:
- THBru作为RAGE的抑制剂,从而使PI3K/AKT/NF-κB通路失活.
- THBru减轻心肌细胞中的炎症反应和氧化应激,对DCM提供保护作用.
- THBru证明了治疗糖尿病心肌病的治疗潜力.
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