奎尔塞丁和AMPK:通过AMPK/SIRT1/NF-κB通路缓解MG诱导的炎症的动态双重作用
Ziyin Lu1, Haozhen Wang1, Muhammad Ishfaq2
1School of Life Science, Liaoning University, Chongshanzhong-Lu No. 66, Shenyang 110036, China.
Molecules (Basel, Switzerland)
|November 14, 2023
概括
奎尔素通过激活AMPK/SIRT1通路,有效地对抗由Mycoplasma gallisepticum (MG) 引起的鸟类呼吸道疾病. 这种天然化合物可以减少炎症并保护肺部免受损伤,为抗生素提供了一个有希望的替代品.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 兽医医学 兽医医学 兽医医学
背景情况:
- 由于慢性呼吸道疾病,Mycoplasma gallisepticum (MG) 在家禽中造成重大经济损失.
- 抗生素耐药性和临床挑战需要鸟类呼吸道感染的替代治疗方法.
- 包括SIRT1在内的AMP激活蛋白激酶 (AMPK) 途径在细胞能量代谢中发挥作用,并具有抗炎性质.
研究的目的:
- 调查奎尔素作为替代治疗剂对禽类中MG诱导的炎症损伤的潜力.
- 阐明素作用的潜在机制,重点关注AMPK/SIRT1/NF-κB信号通路.
主要方法:
- 使用AlphaFold2预测和分子对接的in silico分析.
- 在体外验证素和AICAR对肉AMPKγ1亚单元激活的影响.
- 在MG感染的中体内评估奎尔素的疗效,包括肺形态学,免疫组织化学和炎症标志物分析.
主要成果:
- 奎尔塞丁和AICAR表现出类似的AMPKγ1亚单元的激活,在细胞水平上得到证实.
- 奎尔丁治疗显著降低了促炎性细胞因子 (IL-1β,TNF-α,IL-6) 和改善了MG感染的气囊和肺损伤.
- 奎尔提升了酸化AMPK和SIRT1水平,同时降低了酸化P65和促炎因素,表明AMPK/SIRT1/NF-κB通路的调节.
结论:
- 该AMPK级联信号通路被确定为奎尔素抗炎作用的关键调解者,可以对抗MG诱导的呼吸系统损伤.
- 奎尔因通过向AMPK通路,显示出作为治疗鸟类呼吸系统疾病的治疗剂的显著潜力.
- 这项研究强调AMPK途径是开发用于家禽的新型抗炎药物的有希望的目标.
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