柏柏林通过RXRα/PPARγ/NEDD4途径抑制了在动脉样硬化中的SASP相关炎症
Yinghong Zheng1,2, Jiayuan Kou3, Xi Gao2
1Department of Pharmacology, Tianjin Medical University 22 Qixiangtai Road, Heping District, Tianjin 300070, P. R. China.
The American journal of Chinese medicine
|January 20, 2025
概括
柏柏林 (BBR) 通过向RXRα/PPARγ/NEDD4通路来对抗动脉样硬化中的衰老细胞炎症. 这种天然化合物可以减少老化相关的分泌表型 (SASP) 和小鼠模型中的斑块进展.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 药理学 药理学是指药理学的学科.
背景情况:
- 累积的衰老细胞,特别是动脉样硬化斑块中的泡细胞,驱动慢性炎症.
- 柏柏林 (BBR) 已知可以抑制细胞衰老,但其精确的动脉样硬化机制尚不清楚.
- 了解BBR对老化相关分泌表型 (SASP) 的影响对于治疗开发至关重要.
研究的目的:
- 阐明Berberine (BBR) 治疗动脉样硬化衰老的分子机制.
- 研究RXRα/PPARγ/NEDD4信号通路在BBR抗衰老作用中的作用.
- 评估BBR在动脉样硬化小鼠模型中的治疗潜力.
主要方法:
- 在食高脂肪饮食的ApoE-/-小鼠中诱导了动脉样硬化,随后进行BBR治疗.
- 分析了斑块形态和血液化学;在巨细胞中检测到与SASP相关的蛋白质.
- 智能-seq和lentivirus介导的RXRα敲除被用来探索信号通路和验证发现.
主要成果:
- BBR治疗减少了动脉样硬化斑块负担和与SASP相关的炎症.
- BBR激活了RXRα/PPARγ/NEDD4通路,促进了GATA4/p62复合体的泛化和降解.
- 针对巨细胞的RXRα抑制消除了BBR的抗动脉样硬化和抗衰老作用.
结论:
- 柏柏林 (BBR) 通过RXRα/PPARγ/NEDD4通路减轻动脉样硬化中SASP相关的炎症.
- BBR增强了巨细胞无处不在的过程,导致减少炎症蛋白质的产生.
- 使用BBR准RXRα通路,为动脉样硬化提供了一个有前途的治疗策略.
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