Oxycodone alleviates post-anaesthesia 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 anaesthetics, but its mechanism is unknown. This study probes microRNA (miR)-150-5p's possible role.2. Preoperative and postoperative serum samples were obtained from elderly patients, categorised into the POCD and non-POCD groups after oxycodone anaesthesia. 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 cell 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 anaesthesia.