To explore the neuroprotective effect of polydatin on fentanyl anesthesia and its potential mechanism.Isolate mouse hippocampal neurons for culture and treat them with fentanyl,polydatin + fentanyl,polydatin + fentanyl + IgG,polydatin + fentanyl + MNAC13(TrkA blocking antibody),and then the apoptosis was detected by TUNNEL,the expression of Caspase-9 and tropomyosin receptor kinase(Trk) receptor was detected by immunohistochemistry,and through the Morris water maze test to detect the learning and memory ability of mice treated with fentanyl,fentanyl and polydatin.The results showed that pretreatment with polydatin can significantly increase TrkA phosphorylation and inhibit apoptosis,while MNAC13 can significantly inhibit TrkA phosphorylation and induce apoptosis;in addition,compared with control mice,fentanyl mice learning and memory abilities decreased significantly,and polydatin treatment can significantly improve the learning and memory abilities of mice.The above results show that polydatin can inhibit fentanyl-induced apoptosis of hippocampal neurons,play a neuroprotective role,and improve the learning and memory abilities of mice.