Lidocaine intervention attenuated postoperative delirium by reshaping intestinal flora and modulating microglia M2 type polarization and blood-brain barrier.

Postoperative delirium (POD) is a prevalent postoperative complications among the elderly. Lidocane (LID), a sodium channel blocker, has protective effects on intestinal barrier dysfunction and cognitive impairment, however, with unclear specific mechanism in POD. Eighteen C57BL/6J mice were randomized into the Sham, POD (surgical and anaesthetic exposure), and POD + LID (8 mg/kg) groups (n = 6). Behavioral assessments, including open-field, Y-maze, and buried food tests pre-treatment and post-treatment were conducted. HE and Golgi-Cox staining of hippocampus tissues, FITC-Dextran for blood-brain barrier (BBB) permeability, and 16S rRNA sequencing for intestinal flora were performed. In vitro, mouse microglial cell line BV2 cells were randomized into the Control, LPS (100 ng/mL), and LPS + LID (10 μg/mL) groups. CD86 and CD206 expression was measured by flow cytometry. ELISA for inflammatory factors, immunofluorescence, qRT-PCR, and Western blot for microglia polarization and tight junction markers of mice and cells were performed. Compared to the POD group, the POD + LID group improved spatial learning and memory capacity, increased dendritic spine density, CD206, arginase-1, IL-10, zonula occludens-1, occludin, and claudin-5 expression, and decreased pathological damage, BBB permeability, ionized calcium binding adapter molecule 1, inducible nitric oxide synthase, CD86, TNF-α, IL-1β, and IL-6 expression. The g_Prevotellaceae_UCG_001, g_Rikenellaceae_RC9_gut_group, and g_Faecalibaculum were potential markers of LID intervention in POD. In vitro, the LPS + LID group exhibited the same above effects, with higher cyclooxygenase-2 and lower Chitinase-3 like-protein-1 expression. LID intervention may attenuate POD by modulating intestinal flora, promoting microglia M2 type polarization, and restoring BBB, offering a theoretical basis for its clinical application in POD treatment.