特里普托利德通过调节USP14/Keap1/Nrf2通路来抑制热致死和EndMT来减弱心脏重塑
Lina Ba1,2, Mingyao E2,3, Ruixuan Wang2
1Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
Heliyon
|January 31, 2024
概括
托利德 (TP) 通过抑制热和内皮细胞转移到介质细胞转变 (EndMT) 来减少心脏重塑. 这种天然化合物向USP14/Keap1/Nrf2通路,为心脏病提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 药理学 药理学是指药理学的学科.
- 分子医学是分子医学.
背景情况:
- 心脏重塑,其特点是缩和纤维化,是各种心脏疾病的标志.
- 来自Tripterygium wilfordii Hook F的天然化合物Triptolide (TP) 在治疗心脏病方面具有潜力,但其确切的机制尚不清楚.
研究的目的:
- 阐明Triptolide (TP) 减轻心脏重塑的机制.
- 调查TP对心脏热的作用,内皮转移到介质酶转移 (EndMT),以及潜在的分子通路.
主要方法:
- 使用横向大动脉收缩 (TAC) 和血管素II (Ang II) 模型用于心脏缩,以及用于EndMT的转化生长因子β1 (TGF-β1) 模型.
- 评估了心脏功能,纤维化和蛋白质表达 (BNP,β-MHC,Col I/III,IL-1β,IL-18,Nrf2,HO-1). 通过心脏功能,纤维化和蛋白质表达 (BNP,β-MHC,Col I/III,IL-1β,IL-18,Nrf2,HO-1) 的评估.
- 使用siRNA来静止Nrf2和Ubiquitin-Specific Protease 14 (USP14),以及网络药理学和共免疫沉 (CoIP) 试验.
主要成果:
- TP改善了心脏功能,减少了心肌细胞大小,纤维化,并抑制了热和EndMT.
- 提升TP的调节 核因子红色素2相关因子2 (Nrf2) 和血红氧酶1 (HO-1);Nrf2沉默取消了TP的保护作用.
- 通过向USP14/Keap1/Nrf2通路,TP抑制了EndMT,USP14直接与Keap1.1相互作用.
结论:
- 托利德 (TP) 通过减少热致死和EndMT来减轻心脏重塑.
- 该机制涉及针对USP14/Keap1/Nrf2通路,突出显示TP作为心脏重塑的潜在治疗剂.
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