化会通过BMAL1-介导的Nrf2/ARE通路加剧缺血再输损伤
Chong Dong1, Jing Li2, Qiao Tang3
1Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China; Tianjin Key Laboratory for Organ Transplantation, Tianjin, China.
Archives of biochemistry and biophysics
|September 1, 2023
概括
脏缺血破坏脏时钟基因节律,损害了在夜间脏缺血-再输液损伤期间对抗氧化应激和炎症的能力. 这种干扰会加剧损伤.
科学领域:
- 循环节生物学 日间生物
- 脏生理学 脏生理学
- 分子医学是分子医学.
背景情况:
- 时钟基因的昼夜节律影响功能和受伤的易感性.
- 缺血-再输液 (IR) 损伤是一个重要的临床问题,特别是当发生在一天中的特定时间时.
- 损伤 (RDN) 在调节昼夜节律和IR损伤中的作用尚未完全理解.
研究的目的:
- 为了研究损伤如何影响时钟基因节奏.
- 确定改变的时钟基因节律对红外伤害期间功能和氧化应激的影响.
- 阐明涉及Nrf2通路的潜在机制.
主要方法:
- 小鼠在早上7点或晚上7点接受了假手术,RDN,IR或RDN + IR.
- 通过组织学评估功能,血清肌素,尿素,以及与中性粒细胞凝酶相关的利波卡林.
- 氧化应激,炎症和时钟基因 (BMAL1,CLOCK) 和Nrf2通路基因 (Nrf2,HO-1) 的表达是使用生物化学测试和分子技术 (qPCR,Western Blot) 来测量的.
主要成果:
- RDN破坏了BMAL1,CLOCK和Nrf2的脏节奏,但没有显著改变基线功能.
- RDN加剧了脏IR损伤,氧化应激和炎症,特别是在夜间受伤时.
- 在RDN脏中的夜间IR显示出最严重的损伤,具有最高的BMAL1,Nrf2和HO-1表达,表明Nrf2激活受损.
结论:
- 脏缺血破坏了BMAL1介导的脏内Nrf2积累的节奏.
- 这种干扰会降低脏在夜间红外线损伤期间抵抗氧化应激和炎症的能力.
- Nrf2/ARE通路的受损激活有助于在RDN和IR后加重损伤.
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