Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway

作者全名："Zhang, Zheng-tao; Xie, Ke; Luo, Ren-jie; Zhang, Dan-ying; He, Zhi-wei; Li, Ke-feng; Lin, Shi-hui; Xu, Fang"

作者地址："[Zhang, Zheng-tao; Xie, Ke; Luo, Ren-jie; Zhang, Dan-ying; He, Zhi-wei; Li, Ke-feng; Lin, Shi-hui; Xu, Fang] Chongqing Med Univ, Dept Crit Care Med, Affiliated Hosp 1, 1, Youyi Rd, Chongqing City 400016, Peoples R China; [Zhang, Zheng-tao; Xie, Ke; Luo, Ren-jie] Chongqing Key Lab Translat Med Major Metab Dis, Chongqing City, Peoples R China; [Xie, Ke] Chongqing Med Univ, Dept Crit Care Med, Affiliated Hosp 2, Chongqing City, Peoples R China; [Li, Ke-feng] Chongqing Med Univ, Fengjie Hosp, Dept Crit Care Med, A Branch,Affiliated Hosp 2, Chongqing City, Peoples R China"

通信作者："Xu, F (通讯作者)，Chongqing Med Univ, Dept Crit Care Med, Affiliated Hosp 1, 1, Youyi Rd, Chongqing City 400016, Peoples R China."

来源：INFLAMMOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000900931700001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Dexmedetomidine; Acute respiratory distress syndrome; Acute lung injury; Regulatory T cells; AMP-activated protein kinase; Sirtuin1

摘要："Objectives To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI. Materials and Methods C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine. Results Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naive CD4(+)T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells. Conclusions DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naive CD4(+)T cells via activating the AMPK/SIRT1 pathway."

基金机构：project of Chongqing Postgraduate Research and Innovation [CYS21215]; National Natural Science Foundation grants of China [8217216]; Joint project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission [2020GDRC001]; Clinical Medicine Postgraduate Joint Training Base of Chongqing Medical University-the First Affiliated Hospital of Chongqing Medical University [lpjd202001]; project of Chongqing talents [cstc2022ycjh-bgzxm0131]

基金资助正文："This research was supported by the project of Chongqing Postgraduate Research and Innovation (CYS21215, to ZT Zhang and F Xu), National Natural Science Foundation grants of China (8217216, to F Xu), the Joint project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission (2020GDRC001 to F Xu), and Clinical Medicine Postgraduate Joint Training Base of Chongqing Medical University-the First Affiliated Hospital of Chongqing Medical University (lpjd202001), and the project of Chongqing talents(cstc2022ycjh-bgzxm0131 to F Xu)."