Role of α7nAChR in postoperative cognitive dysfunction in aged rats with tibial fracture

Abstract

Objective To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in postoperative cognitive dysfunction in aged rats with tibial fracture. Methods One hundred and fifty clean-grade healthy male Sprague-Dawley rats, aged 18-22 months, weighing 440-580 g, were divided into 5 groups (n=30 each) using a random number table method: control group (group C), sham operation group (group S), tibial fracture group (group T), normal saline group (group N) and α7nAChR agonist PUN282987 group (group P). Group C received no treatment.Ten percent chloral hydrate 0.4 ml/100 g was injected intraperitoneally in group S. Group T underwent tibial fracture.PUN282987 2.4 mg/kg was intraperitoneally injected at 5 min before tibial fracture in group P. The equal volume of normal saline was given at 5 min before tibial fracture in group N. Morris water maze test was performed at day 7 after surgery.At days 1, 3 and 7 after surgery, the pathological changes of the hippocampal CA3 region were observed by haematoxylin and eosin staining, and the expression of α7nAChR, choline acetyltransferase (ChAT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampal CA3 region was measured by Western blot. Results Compared with group C, the postoperative escape latency and swimming distance were significantly prolonged, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point after operation in T, N and P groups (P 0.05). Compared with group T, the postoperative escape latency and swimming distance were significantly shortened, and the expression of α7nAChR and ChAT was up-regulated and the expression of TNF-α and IL-1β was down-regulated at each time point after operation in group P (P 0.05), and the pathological changes of the hippocampal CA3 region were significantly attenuated in group P. Conclusion α7nAChR antagonism is involved in the development of postoperative cognitive dysfunction in aged rats with tibial fracture. Key words: Cholinergic agonists; Aged; Cognition disorders; Postoperative complications