Role of connexin43 in sevoflurane-induced cognitive dysfunction in aged rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of connexin43 (Cx43) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods:Fifty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 400-500 g, were divided into 4 groups ( n=13 each) using a random number table method: control group (C group), sevoflurane group (SEV group), sevoflurane plus sh-NC group (SEV+ sh-NC group) and sevoflurane plus sh-Cx43 group (SEV+ sh-Cx43 group). Sevoflurane anesthesia model was established by inhaling 3% sevoflurane for 6 h. In SEV+ sh-NC group and SEV+ sh-CX43 group, sh-NC 5 nmol and sh-CX43 5 nmol were transfected into the lateral ventricles, respectively, at 1 day before sevoflurane anesthesia.Morris water maze test was performed at 30 min before anesthesia and 1, 2 and 3 days after the end of anesthesia, and the rats were sacrificed at each time point after Morris water maze test, the brains were removed, and the hippocampi were isolated for microscopic examination of the pathological changes and for determination of the expression of Cx43, cleaved caspase-3 and cleaved caspase-9 (by using Western blot), and contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group C, the escape latency was significantly prolonged, and the number of crossing the original platform was reduced, and the expression of CX43, cleaved caspase-3 and cleaved caspase-9 was up-regulated, and the contents of IL-1β, TNF-α and IL-6 were increased in group SEV ( P<0.05). Compared with group SEV, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the expression of CX43, cleaved caspase-3 and cleaved caspase-9 was down-regulated, the contents of IL-1β, TNF-α and IL-6 were decreased ( P<0.05), and the hippocampal pathological injury was reduced in group SEV+ sh-CX43, and no significant change was found in the indicators mentioned above in group SEV+ sh-NC ( P>0.05). Conclusion:Cx43 is involved in the pathophysiological mechanism of sevoflurane-induced cognitive dysfunction probably by inducing neuroinflammatory responses and cell apoptosis in aged rats.