Oxycodone Alleviates Post-anesthesia Cognitive Impairment in the Elderly via miR-150-5p/H731 axis

1. Postoperative cognitive dysfunction (POCD) is a major issue in elderly surgical patients. Oxycodone (Oxy) reduced POCD risks versus other anesthetics, but its mechanism is unknown. This study probes miR-150-5p's possible role.2. Preoperative and postoperative serum samples were obtained from elderly patients, categorized into the POCD and non-POCD groups after oxycodone anesthesia. In vivo POCD mice and in vitro LPS-induced cell models were constructed, both treated with Oxy. miR-150-5p levels were measured by RT-qPCR. ROC curve evaluated its diagnostic potential for POCD. Morris Water Maze tested spatial learning/memory in POCD mice. Flow cytometry assessed apoptosis.3. At baseline, miR-150-5p and Nuclear Antigen H731 (H731) levels were similar between groups; however, at 72 h post-op, the POCD group had lower miR-150-5p and higher H731. MiR-150-5p acted as a risk factor and effective biomarker for identifying elderly patients at high risk of POCD. Oxy alleviated hippocampal injury and cognitive deficits in aged POCD mice, which were reversed by miR-150-5p knockdown but restored by H731 depletion. miR-150-5p knockdown abolished Oxy-mediated protection against apoptosis, inflammation, and oxidative stress, whereas H731 silencing rescued such effects.4. miR-150-5p served as a diagnostic biomarker in elderly patients undergoing Oxy-under general anesthesia.