Relationship between NMDA receptor and postoperative fatigue syndrome and its associated central mechanism

Objective To explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism. Methods After being numbered according to the weight, ninety-six male SD rats were randomly divided into control group(bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg), POFS model(70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups(70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test(OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase Ⅲ(KAT Ⅲ) by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography(HPLC) was used to measure the concentrations of tryptophan(TRP), kynurenine(KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy(TEM). Results As compared to control group, exercise score decreased(P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased(all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased(P<0.05), mRNA expression of KAT Ⅲ decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased(all P <0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1, and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3(all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats, while such damage was improved in antagonist group. Conclusion The increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS. Key words: Postoperative fatigue syndrome; NMDA receptor; Tryptophan; Kynurenine; Rats