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通过PI3K-Akt途径对因败血症引起的肺损伤产生人参化物Rg1的保护作用:来自分子动力学模拟和实验验证的见解
Kaiqiang Zhong1, Yingui Huang1, Rui Chen2,3
1Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Scientific reports
|July 11, 2024
概括
金色化物Rg1 (GRg1) 通过减少炎症和亡,有效地治疗败血症引起的急性肺损伤 (SALI). 这种传统医学化合物向AKT1,激活PI3K-AKT通路,以提高SALI小鼠模型的生存率.
科学领域:
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 败血症引起的急性肺损伤 (SALI) 是一种具有高死亡率的严重疾病.
- 来自传统中医药的金色化物Rg1 (GRg1) 显示出对肺细胞的抗炎和保护作用.
- GRg1在缓解SALI中的精确机制需要进一步研究.
研究的目的:
- 在SALI小鼠模型中阐明GRg1的治疗机制.
- 通过网络药理学和分子对接,识别GRg1的分子标.
- 在实验室中验证GRg1在保护肺上皮细胞和减少炎症中的作用.
主要方法:
- 败血症引起的急性肺损伤 (SALI) 鼠标模型和体外MLE-12细胞培养.
- 网络药理学,分子对接和分子动力学模拟以确定目标.
- 定量实时PCR (qRT-PCR),西斑和流细胞计用于机械学研究.
- 使用LY294002抑制AKT1以确认途径的参与.
主要成果:
- 在CLP诱导的SALI小鼠中,GRg1治疗缓解了肺损伤,减少了促炎性细胞因子 (IL-6,TNF-α,IL-1β) 和改善了生存率.
- 网络药理学确定了116个共同目标,其中AKT1,VEGFA,SRC和STAT3是核心目标.
- 在LPS刺激的MLE-12细胞中,GRg1通过增加Bcl-2/Bax比率,减少分裂的caspase-3和激活PI3K-AKT通路来抑制细胞亡.
- 分子动力学证实了GRg1与AKT1的有利结合,而AKT1的抑制则否定了GRg1的保护作用.
结论:
- 金色化物Rg1在败血症引起的急性肺损伤中显示出显著的治疗潜力.
- GRg1通过抑制膜上皮细胞中的亡并减少炎症来发挥保护作用.
- 特别针对AKT1的PI3K-AKT通路是GRg1在SALI中的有益作用的关键调解者.
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