AdipoRon Inhibits Neuroinflammation Induced by Deep Hypothermic Circulatory Arrest Involving the AMPK/NF-κB Pathway in Rats
Weidong Yan,
Sizhe Gao,
Qiaoni Zhang,
Jiachen Qi,
Gang Liu,
Yuan Teng,
Jian Wang,
Shujie Yan,
Bingyang Ji
Affiliations
Weidong Yan
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Sizhe Gao
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Qiaoni Zhang
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Jiachen Qi
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Gang Liu
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Yuan Teng
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Jian Wang
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Shujie Yan
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Bingyang Ji
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Disease, State Key Laboratory of Cardiovascular Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
Deep hypothermic circulatory arrest (DHCA) can induce systemic inflammatory response syndrome, including neuroinflammation. Finding suitable compounds is necessary for attenuating neuroinflammation and avoiding cerebral complications following DHCA. In the present study, we established DHCA rat models and monitored the vital signs during the surgical process. After surgery, we found significantly increased proinflammatory cytokines (IL-6, IL-1β, and TNF-α) in DHCA rats. Quantitative proteomics analysis was performed for exploring the differentially expressed proteins in hippocampus of DHCA rats and the data showed the adiponectin receptor 1 protein was upregulated. More importantly, administration of AdipoRon, a small-molecule adiponectin receptor agonist, could improve the basic vital signs and attenuate the increased IL-6, IL-1β, and TNF-α in DHCA rats. Furthermore, AdipoRon inhibits the activation of microglia (M1 state) and promotes their transition to an anti-inflammatory state, via promoting the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), and downregulating nuclear factor kappa B (NF-κB) in DHCA rats. Consistently, we used LPS-treated BV2 cells to mimic the neuroinflammatory condition and found that AdipoRon dose-dependently decreased cytokines, along with increased phosphorylation of AMPK and downregulated NF-κB. In conclusion, our present data supported that AdipoRon inhibited DHCA-induced neuroinflammation via activating the hippocampal AMPK/NF-κB pathway.
