帕尔马丁可以通过激活EGFR通路通过上调IKBKBB来逆转阿里斯托洛基酸诱导的心力衰竭
Ying Hu1, Lixin Chen1, Yulin Wu1
1Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, Jiangxi 341000, China.
Ecotoxicology and environmental safety
|September 27, 2024
概括
阿里斯托洛希酸会导致心力衰竭,但棕酸治疗可以恢复心脏功能. 帕尔马丁通过上调表皮生长因子受体 (EGFR) 途径来起作用,提供了一个潜在的治疗点.
科学领域:
- 毒理学 毒理学 毒理学
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 阿里斯托洛基酸 (AA) 已知具有毒性和致性,新出现的证据将其通过炎症途径与心力衰竭 (HF) 联系起来.
- 基于AA诱导的心脏毒性和潜在的治疗干预的精确机制在很大程度上仍未被探索.
研究的目的:
- 用斑马鱼模型研究阿里斯托洛希酸 (AA) 的心脏毒性.
- 评估植物性类化合物帕尔马丁 (PAL) 对AA诱导的心脏损伤的修复作用.
- 阐明帕尔马丁对抗AA诱导心力衰竭的治疗作用的潜在分子机制.
主要方法:
- 斑马鱼模型用于AA诱导心脏毒性评估.
- 组织学分析 (o-dianisidine染色,光成像,Hematoxylin和Eosin染色) 以评估心脏形态和血液供应.
- 生物化学测定ATPase活性和中性粒细胞-心肌细胞共同定位.
- 网络药理学分析,qPCR验证,转录学测试,抑制剂模型和分子对接以确定治疗途径.
主要成果:
- 帕尔马丁 (PAL) 恢复了AA损坏的斑马鱼心脏中的心脏形态和血液供应.
- PAL减弱了AA诱导对ATPase活性的有害影响,表明心肌能量代谢的恢复.
- 帕尔减少了中性粒细胞的透,表明减轻了炎症反应.
- 网络药理学和验证确定了表皮生长因子受体 (EGFR) 信号通路作为关键,PAL作为IKBKB酶激活剂.
结论:
- 在斑马鱼模型中,帕尔马丁 (PAL) 显示出显著的心脏保护作用,防止阿里斯托洛希克酸 (AA) 诱导的心力衰竭.
- 治疗机制涉及表皮生长因子受体 (EGFR) 信号通路的上调和IKBKB的激活.
- EGFR途径为开发针对AA诱导心脏毒性的保护性药物提供了潜在的治疗标.
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