Abstract:

Objective To explore the role of MAGI2⁃AS3/miR⁃374b⁃5p/HOXB7 axis in the pathogenesis of sepsis⁃associated encephalopathy（SE）. Methods Sepsis was induced in adult C57BL/6J male mice by cecal ligation and perforation（CLP）surgery. Randomly selected CLP mice were transfected with short interfering RNAs （siRNAs）against MAGI2⁃AS3，or with miR⁃374b⁃5p mimics and related controls. Cognitive behavior was tested 8 ~ 12 days after the surgery using a Morris water maze. Hippocampal neuronal apoptosis indicators in CLP mice were then detected. The hippocampal neuron damage model was induced by LPS. Next，the neurons were，respec⁃ tively，transfected with si⁃MAGI2⁃AS3 or miR⁃374b⁃5p mimics to determine the proliferation inhibition and apopto⁃ sis of hippocampal neurons. The interactions between MAGI2⁃AS3，miR⁃374b⁃5p and HOXB7 were assessed using dual luciferase reporter gene assay. Results CLP mice showed progressive increases in MAGI2⁃AS3 levels and progressive decreases in miR ⁃374b ⁃5p levels on the 3rd，7th，and 14th after CLP surgery，accompanied by im⁃ paired cognitive function. MAGI2⁃AS3 silencing and miR⁃374b⁃5p elevation improved spatial learning ability and memory ability，and depressed neuronal apoptosis in CLP mice. MAGI2⁃AS3 silencing and miR⁃374b⁃5p elevation increased viability and limited apoptosis of LPS ⁃treated hippocampal neurons. MAGI2⁃AS3 specifically bound to miR⁃374b⁃5p，and miR⁃374b⁃5p targeted HOXB7. Conclusion MAGI2⁃AS3 silencing inhibits the apoptosis of hippocampal neurons in CLP mice by up⁃regulating miR⁃374b⁃5p and down⁃regulating HOXB7. 

Key words:

lncRNA MAGI2?AS3, miR?374b?5p, HOXB7, cecal ligation and perforation, mice