Role of hippocampal histone deacetylases in perioperative neurocognitive disorders in rats and the relationship with PSD95 / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of hippocampal histone deacetylases (HDACs) in perioperative neurocognitive disorders (PND) and the relationship with postsynaptic dense protein 95 (PSD95) in rats.Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 10-14 weeks, weighing 250-280 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), surgery group (group S) and HDAC inhibitor MS-275 group (group MS-275). Exploratory laparotomy was performed under 3% sevoflurane anesthesia in group S. MS-275 10 mg/kg was intraperitoneally injected at 0.5 h before exploratory laparotomy in group MS-275.Morris water maze tests were performed on 1 day before surgery and 1, 3 and 7 days after surgery.Ten rats were sacrificed on 1 day after surgery, and hippocampal tissues were obtained for determination of the expression of HDAC1-3 and PSD95 protein and mRNA by Western blot and real-time polymerase chain reaction, respectively.The density of hippocampal neurons was determined by the Nissl staining. Results:Compared with group C, the postoperative escape latency was significantly prolonged, the number of crossing the original platform was decreased, the density of hippocampal neurons was decreased, the expression of HDAC2 protein and mRNA was up-regulated, and the expression of PSD95 protein and mRNA was down-regulated in group S ( P<0.05 or 0.01). Compared with group S, the postoperative escape latency was significantly shortened, the number of crossing the original platform was increased, the density of hippocampal neurons was increased, the expression of HDAC2 protein and mRNA was down-regulated, and the expression of PSD95 protein and mRNA was up-regulated in group MS-275 ( P<0.05 or 0.01). There was no significant difference in the expression of HDAC1 and HDAC3 protein and mRNA among the three groups ( P>0.05). Conclusion:HDAC2 is involved in the pathophysiological mechanism of PND by down-regulating the expression of PSD95 in rats.