亚西化物通过抑制RhoF-NF-κB/MAPK信号和巨细胞炎症来缓解动脉样硬化的进展
Junlu Wang1, Lingli Lei2, Shasha Wang3
1State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China.
概括
亚西胺 (AT) 通过减少炎症和稳定斑块,有效治疗动脉样硬化 (AS). 它通过降解RhoF蛋白来起作用,抑制关键的炎症途径,如NF-κB和MAPK.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 来自Centella asiatica的亚洲化 (AT) 具有已知的抗炎性质.
- 动脉样硬化 (AS) 是一种慢性炎症疾病,治疗选择有限.
- 需要进一步研究AT在改善AS方面的精确机制.
研究的目的:
- 为了评估亚西胺 (AT) 的抗动脉样硬化作用.
- 阐明AT在动脉样硬化的治疗作用背后的分子机制.
- 识别AS中AT调节的关键分子标和途径.
主要方法:
- 在体内研究中,使用高脂肪饮食诱导的AOE-/-小鼠接受了AT或他类药物治疗.
- 在体外研究中,氧化低密度脂蛋白 (Ox-LDL) 刺激的腹巨细胞.
- 网络药理学,RNA测序 (RNA-Seq),分子对接,SPR,Western blotting,IHC和免疫光学,以识别和验证AT目标和途径.
主要成果:
- 在ApoE-/-小鼠中,AT治疗显著降低了AS的进展,并提高了斑块稳定性.
- 在体内和体外模型中,AT通过减少巨细胞透来抑制炎症.
- 网络药理学和RNA-Seq确定RhoF是关键目标,AT促进其蛋白质体降解并抑制NF-κB/MAPK信号传递.
结论:
- 亚西化物 (AT) 缓解AS进展,并通过通过RhoF蛋白质体降解和NF-κB/MAPK通路抑制抑制炎症来增强斑块稳定性.
- 针对蛋白质稳定性的AT机制可能比现有的抗炎药物具有优势.
- 作为一种抗动脉样硬化治疗剂,AT显示出显著的潜力,这需要进一步的临床研究.
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