关键词: 淫羊藿苷, 认知功能障碍, 海马神经元, 凋亡, 七氟醚

Abstract: Objective To evaluate the effect of icariin on sevoflurane-induced postoperative cognitive dysfunction (POCD),and to explore its potential mechanism. Methods The mice were divided into control group, model group(sevoflurane anesthesia + laparotomy were used to establish a mouse POCD model), icariin group, PI3K inhibitor group, icariin + inhibitor group, PI3K activator group, with 12 rats in each group. Conditional fear test and Y maze test were used to evaluate cognitive dysfunction in mice; ELISA method was used to detect the levels of serum TNF-α, IL-1β and BDNF; the hippocampal tissue was taken, Nissl staining was used to observe the changes of neuron morphology; TUNEL staining was used to detect neuronal apoptosis rate; the expression levels of M1 and M2 activated microglia and their markers were detected by immunofluorescence method; Western blot was used to detect the expression of TNF-α, IL-1β,IL-10, GSK-3β phosphorylated protein and Bcl-2. Results Compared with the control group, mice of model group showed cognitive impairment, severe hippocampal neuron impairment and apoptosis, the pro-inflammatory response mediated by M1 polarization of microglia in the hippocampus was more intensive than the anti-inflammatory response mediated by M2 polarization. The expression of PI3K/Akt-GSK-3β pathway and its mediated anti-inflammatory and anti-apoptotic proteins decreased (P＜0.05). Icariin and PI3K activator intervention promoted the PI3K/Akt-GSK-3β pathway and its anti-inflammatory and anti-apoptotic responses, and promote the anti-inflammatory response mediated by M2 polarization of hippocampal microglia, alleviated the impairment and apoptosis of hippocampal neurons, and improved cognitive function impairment of mice (P＜0.05). PI3K inhibitors could weaken the above-mentioned effects of icariin (P＜0.05). Conclusions The effect of icariin on improving the apoptosis of hippocampal neurons and cognitive impairment in POCD mice may be related to promoting the activation of PI3K/Akt pathway and enhancing the anti-inflammatory response mediated by M2 polarization of microglia.

Key words: icariin, cognitive dysfunction, hippocampal neurons, apoptosis, sevoflurane