ресвератрол通过Sirt1/p53通路激活抑制铁和减缓心力衰竭的进展
Wei Zhang1, Shaohuan Qian1, Bi Tang1
1Department of Cardiovascular Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, China.
Journal of cellular and molecular medicine
|July 24, 2023
概括
Ресвератрол通过激活Sirt1/p53通路来保护心脏,抑制铁亡,并在心力衰竭模型中改善心脏功能. 这种机制涉及调节SLC7A11和谷氨水平.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 心力衰竭是一种复杂的疾病,具有显著的发病率和死亡率.
- 铁亡是一种受调节的细胞死亡形式,在心力衰竭的进展中起作用.
- 复星是一种具有潜在治疗益处的天然化合物.
研究的目的:
- 为了研究复星的心脏保护作用.
- 为了确定复星是否通过Sirtuin 1 (Sirt1) / p53通路抑制铁亡.
- 为了阐明背后的分子机制 复星在心力衰竭的作用.
主要方法:
- 在Sirt1淘汰赛小鼠中通过大动脉缩建立了心力衰竭模型.
- 评估了铁亡的标志物 (超氧化物脱酶,谷氨),线粒体形态和心脏功能 (BNP,sST2,心声回声).
- 利用人类诱导的多能干细胞干细胞衍生心肌细胞 (hiPSC-CMs) 进行基因操纵 (p53突变,Sirt1干扰) 和免疫沉.
主要成果:
- 在心力衰竭模型中,复星改善了心脏功能,减少了铁和纤维化.
- 在Sirt1沉默后,复星的心脏保护作用被废除了.
- 通过白醇激活Sirt1,降低了p53乙化,阻止了SLC7A11降解,并增加了谷氨 (GSH) 和谷氨过氧化酶4 (GPX4) 水平,从而抑制了铁亡.
结论:
- 通过激活Sirt1/p53通路,白醇在心力衰竭中发挥心脏保护作用.
- 这种激活抑制铁灭,可能通过调节p53乙化和SLC7A11表达.
- 复星在心力衰竭中的治疗潜力是通过其通过Sirt1/p53轴预防铁亡的能力来调解的.
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