Effects of vagus nerve stimulation on postoperative cognitive dysfunction and role of hippocampal insulin growth factor 1 signaling pathway in aged mice / 中华麻醉学杂志

ABSTRACT

Objective:To investigate the effects of vagus nerve stimulation on postoperative cognitive dysfunction and the role of hippocampal insulin growth factor 1 signaling pathway in aged mice.Methods:Seventy-five clean-grade C57 mice of both sexes, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O), operation + vagus nerve stimulation group (group O+ V), operation + IGF-1 siRNA group (group O+ I) and operation + vagus nerve stimulation + IGF-1 siRNA group (group O+ V+ I). Group O underwent exploratory laparotomy.Group O+ V received a 30-min electrical stimulation of the vagus nerve (intensity 0.5 mA, frequency 20 Hz, time 30 s, 6 times, interval 5 min) after the end of exploratory laparotomy.Group O+ I underwent exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Group O+ V+ I underwent electrical vagus nerve stimulation after exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Morris water maze tests were performed on 14-18 days after operation.On day 7 after operation, the mice were sacrificed and the hippocampus was obtained for determination of the expression of Bax, ionized calcium-binding adapter molecule 1 (Iba-1), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF1R), phosphorylated IGF1R (p-IGF1R), interleukin-1beta (IL-1β) and activated caspase-3 by Western blot. Results:Compared with group S, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 16-18 after operation, the frequency of crossing the platform was increased, the time spent in the target quadrant was prolonged, the expression of IGF-1 and p-IGF1R was up-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was down-regulated in group O+ V ( P<0.05), and no significant change was found in the parameters mentioned above in group O+ I ( P>0.05). Compared with group O+ V, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O+ V+ I ( P<0.05). There was no significant difference in the expression of IGF1R among the four groups ( P>0.05). Conclusions:Vagus nerve stimulation can reduce postoperative cognitive dysfunction, and the mechanism is related to activation of IGF-1 signaling pathway and reduction of hippocampal neuroinflammation and neuronal apoptosis in aged mice.