Effect of dexmedetomidine on mTOR/tau protein signaling pathway in hippocampus of aged rats after splenectomy

Objective To evaluate the effect of dexmedetomidine on the mammalian target of rapamycin(mTOR)/tau protein signaling pathway in the hippocampus of aged rats after splenectomy. Methods One hundred and fifty pathogen-free healthy male Sprague-Dawley rats, aged 18 months, weighing 400-540 g, were divided into 5 groups(n=30 each)using a random number table: control group(group C), sham operation group(group S), operation group(group O), normal saline group(group NS)and dexmedetomidine group(group D). Group C received no treatment.Ten percent chloral hydrate 0.3 ml/100 g was injected intraperitoneally in group S. Group O underwent splenectomy.Dexmedetomidine 50 μg/kg was injected intraperitoneally at 5 min before splenectomy in group D. The equal volume of normal saline was injected intraperitoneally at 5 min before splenectomy in group NS.Morris water maze test was performed at day 7 after surgery.At days 1, 3 and 7 after surgery, the rats were sacrificed, and the hippocampi were removed for examination of the pathological changes in the hippocampal CA3 region and for determination of the expression of mTOR protein and mRNA, tau protein mRNA and phosphor-tau protein(pS396 tau protein)(by real-time polymerase chain reaction or Western blot). Results Compared with group C, the escape latency and swimming distance were significantly prolonged, and the expression of mTOR protein and mRNA, tau protein mRNA and pS396 tau protein was up-regulated in O, D and NS groups(P 0.05). Compared with group O, the escape latency and swimming distance were significantly shortened, and the expression of mTOR protein and mRNA, tau protein mRNA and pS396 tau protein was down-regulated in group D(P 0.05). The pathological changes in the hippocampal CA3 region were significantly attenuated in group D as compared with group O. Conclusion The mechanism by which dexmedetomidine improves postoperative cognitive function may be associated with inhibited activation of mTOR/tau protein signaling pathway in the hippocampus of aged rats. Key words: Dexmedetomidine; Receptor-interacting protein serine-threonine kinases; tau proteins; Aged; Cognition disorders; Postoperative complications