The miR‑339‑3p/CIZ1 axis is associated with LPS‑induced microglial injury and sevoflurane‑associated cognitive impairment in aged rats

Abstract

Postoperative cognitive dysfunction (POCD) substantially impairs the quality of life in elderly patients, but its underlying molecular mechanisms remain largely elusive. This study aimed to investigate miR‑339‑3p expression and its functional role in LPS‑induced microglial injury in vitro and in sevoflurane (Sev)‑associated cognitive impairment in aged rats. qRT‑PCR and Western blot were used to measure the expression of miR‑339‑3p and CDKN1A-interacting zinc finger protein 1 (CIZ1). Cell viability and apoptosis were assessed using CCK‑8 and flow cytometry assays. Commercial kits were used to assess the concentrations of LDH, MDA, and SOD. ELISA was performed to detect the production of TNF‑α, IL‑1β, and IL‑6. RNA pull‑down and luciferase reporter assays were conducted to validate the direct binding between miR‑339‑3p and CIZ1. Sev exposure was performed in aged rats to establish an anesthesia‑associated cognitive impairment model, while cognitive function was evaluated via the Morris water maze. LPS stimulation increased miR‑339‑3p levels in BV‑2 cells, whereas miR‑339‑3p inhibition partially restored LPS-reduced cell viability and attenuated LPS‑induced increases in apoptosis, oxidative stress, and inflammation. miR‑339‑3p directly targeted CIZ1, and CIZ1 silencing abolished the protective effects conferred by miR‑339‑3p inhibition. miR‑339‑3p inhibition attenuated cognitive impairment in aged rats in vivo, an effect that was reversed by CIZ1 knockdown. miR‑339‑3p inhibition was associated with increased CIZ1 expression and improved behavioral outcomes in Sev‑exposed aged rats, while CIZ1 knockdown attenuated this effect. These findings identify an association between the miR‑339‑3p/CIZ1 axis and Sev‑associated cognitive impairment, warranting further investigation in clinically relevant POCD models.

The authors' abstract, as published at the source. BMC Medical Genomics, 2026 · DOI ↗