Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Molecular Medicine

Hua Fang¹  Miao Yang¹  Wei-Jing Zhang¹  Jian-Ping Zhang¹ 

[1] Department of Anesthesiology, Guizhou Provincial People’s Hospital, No. 83, East Zhongshan Road, 550002, Guiyang, Guizhou, People’s Republic of China;Department of Anesthesiology, Guizhou University People’s Hospital, No. 83, East Zhongshan Road, 550025, Guiyang, Guizhou, People’s Republic of China;Laboratory of Anesthesiology & Perioperative Medicine, Guizhou University School of Medicine, 550025, Guiyang, People’s Republic of China;

关键词: Propofol;    Lung ischemia/reperfusion injury;    Metastasis-associated lung adenocarcinoma transcript;    Microrna-144;    Glycogen synthase kinase-3β;    Autophagy;   

DOI  :  10.1186/s10020-021-00332-0

来源: Springer

【 摘 要 】

BackgroundPropofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β).MethodsC57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured.ResultsOur experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression.ConclusionOverall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

【 授权许可】

CC BY