在绝经后的糖尿病大鼠中,GPER激活通过上调SIRT1/3-AMPK-UCP2通路来减轻心脏功能障碍
Hossein Azizian1, Zeinab Farhadi1, Michael Bader2,3,4,5
1Yazd Neuroendocrine Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
PloS one
|December 22, 2023
概括
通过通过Sirtuin通路改善心脏代谢和功能,GPER激活可以保护绝经后糖尿病大鼠免受心血管疾病的影响. 这表明向锡尔图因水平可能是一个新的治疗策略.
科学领域:
- 心血管科学 心血管科学
- 代谢性疾病研究研究
- 内分泌学 在内分泌学.
背景情况:
- 绝经后糖尿病妇女面临心血管疾病 (CVD) 风险升高.
- 心脏代谢中的Sirtuin变化在这个人群中导致心血管疾病.
- G蛋白结合雌激素受体 (GPER) 显示出潜在的心脏保护作用,但机制尚不清楚.
研究的目的:
- 研究GPER激活在绝经后第二类糖尿病 (T2D) 的大鼠模型中的心脏保护作用.
- 阐明sirtuins和下游通路 (AMPK,UCP2) 在GPER介导的心脏保护中的作用.
主要方法:
- 使用了一个卵巢切除 (OVX) 型二型糖尿病 (T2D) 鼠标模型.
- 使用G-1 (GPER激动剂) 或载体,持续6周.
- 评估了血液动力学因素,心脏蛋白质水平 (sirtuins,p-AMPK,UCP2) 通过西部斑块,以及氧化应激生物标志物.
主要成果:
- 二型糖尿病诱导左心室功能障碍和氧化应激,Sirt1/2/3/6,p-AMPK和UCP2水平降低.
- 更年期状态 (OVX) 加剧了这些心脏功能障碍.
- G-1治疗改善了血液动力学功能,增加了Sirt1/3,p-AMPK,UCP2,并减少了氧化应激.
结论:
- GPER激活在绝经后糖尿病病症中具有心脏保护作用.
- 该机制涉及素 (Sirt1/3),AMP激活蛋白激酶 (AMPK) 和解蛋白2 (UCP2) 途径.
- 调节Sirt1/3水平为绝经后糖尿病心血管疾病提供了潜在的治疗途径.
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