Propofol Rescued Astrocytes from LPS-induced Inflammatory Response via Blocking LncRNA-MEG3/NF-κB Axis

作者：Pingping Xia, Zhi Ye, Fan Zhang, Zhihua Wang, Bei Sun, Yan Huang, Cheng Chen, Jie Hu, Longyan Li · 发表于：Current Neurovascular Research · 年份：2022 · DOI：10.2174/1567202619666220316112509 · 被引用次数：16 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Anesthesia and Neurotoxicity Research、Cancer-related molecular mechanisms research

OBJECTIVE: Evidences demonstrate that propofol attenuates neuro-inflammation following brain ischemia. Moreover, LncRNA-MEG3 has been identified as an independent prognostic marker for ischemic stroke patients, and found to correlate to cerebral ischemia in animal models. Therefore, the current study explored the role of propofol in lipopolysaccharide (LPS)-mediated inflammation in cultured astrocytes, along with the molecular mechanism involved in LncRNAMEG3/ NF-κB axis. METHODS: The primary cultured astrocytes isolated from rats were used to establish an inflammatory model, which were treated with LPS. Propofol was administrated to the primary cultured astrocytes during LPS treatment. The effects of propofol on pro-inflammatory cytokines and the LncRNAMEG3/ NF-κB pathway were detected by ELISA, qRT-PCR and Western Blot assay, respectively. Then, dual-luciferase assay, chromatin immunoprecipitation and RNA immunoprecipitation were used to determine the interaction between LncRNA-MEG3 and NF-κB. RESULTS: Our study found propofol to significantly reduce LncRNA-MEG3 expression, which was elevated in LPS-stimulated astrocytes. Moreover, both propofol and LncRNA-MEG3 knockdown remarkably alleviated LPS-induced cytotoxicity by suppressing expressions and release of proinflammatory cytokines. Loss of LncRNA-MEG3 notably suppressed the NF-κB activity and its phosphorylated activation. Additionally, it was also observed that LncRNA-MEG3 could bind nuclear p65/p50, and promote the bin...