Propofol alleviates postoperative cognitive dysfunction by inhibiting inflammation via up-regulating miR-223-3p in aged rats.

OBJECTIVE

Postoperative cognitive dysfunction (POCD) affects 15-25% of surgical patients and causes significant morbidity and mortality. This study aims to investigate the mechanism of propofol reducing POCD in aged rats.

METHOD

Rats in Operate group and Propofol group were anesthetized with isoflurane and propofol, respectively, and then underwent cardiac surgery. Rats in Antagomir group were anesthetized with propofol and underwent cardiac surgery with preoperative injection of miR-223-3p antagomir. Barnes maze and Morris water maze (MWM) were used to test spatial learning and memory of rats. Immunofluorescence was used to detect the level of microglial cell marker IBA1. In addition, qRT-PCR was performed to measure the expression of miR-223-3p and inflammatory factors TNF-α, IL-1β and IL-6. Western blotting was conducted to detect the protein expression of Foxo1, TNF-α, IL-1β and IL-6.

RESULT

Isoflurane-anesthetized rats undergoing cardiac surgery showed significantly reduced spatial learning and memory, promoted microglia activation, decreased miR-223-3p expression and increased inflammatory response in the hippocampus, while isoflurane-anesthetized rats without surgery showed insignificant changes in these indices. Compared to isoflurane anesthesia, propofol anesthesia exhibited less effect on spatial learning and memory of rats with cardiac surgery and contributed to a relative reduction in activated microglia in the hippocampus, a notable increase in miR-223-3p expression, and a decrease in inflammation. The results were reversed after miR-223-3p antagomir was injected into propofol-anesthetized surgical rats. miR-223-3p negatively regulated Foxo1 to suppress the expression of inflammatory factors.

CONCLUSION

Propofol reduced inflammation by up-regulating miR-223-3p, thereby reducing POCD in aged rats.