Open AccessDexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway
Author(s) -
Wu Yan,
Qiu Gaolin,
Zhang Hainie,
Zhu Leilei,
Cheng Gao,
Wang Yiqiao,
Li Yuanhai,
Wu Weiwei
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16871
Subject(s) - dexmedetomidine , pi3k/akt/mtor pathway , reperfusion injury , protein kinase b , medicine , pharmacology , ischemia , anesthesia , chemistry , signal transduction , biochemistry , sedation
Hepatic ischaemia‐reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR‐494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p‐PI3K, AKT/p‐AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR‐494 expression, and miR‐494 targeted JUND. miR‐494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR‐494/JUND/PI3K/AKT/Nrf2 axis.