Role of PKA-CREB signaling pathway in sevoflurane-induced reduction of cognitive impairment caused by cardiopulmonary bypass in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of protein kinase A (PKA)-cyclic adenosine monophosphate response element binding protein (CREB) signaling pathway in sevoflurane-induced reduction of cardiopulmonary bypass (CPB)-induced cognitive impairment in rats.Methods:Forty healthy male Sprague-Dawley rats, aged 4 months, weighing 300-350 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), group CPB, CPB+ sevoflurane group (group CS) and CPB+ sevoflurane+ PKA inhibitor H89 group (group CSH). After H89 5 μl was injected into the lateral ventricle in group CSH, the rats in group CS and group CSH were exposed to 2.4% sevoflurane for 1 h, and then the CPB model of beating heart without blood priming for 60 min was developed in CPB, CS and CSH groups.The autonomic movement ability was evaluated using the open field test at 2nd day after CPB.Morris water maze test was used to assess the cognitive function at 3rd day after CPB.The rats were sacrificed after the Morris water maze test, the brain was removed and the hippocampal tissues were isolated for determination of the apoptosis rate of hippocampal neurons (by flow cytometry) and expression of PKA, phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF) (by Western blot). Results:There was no significant difference in movement speed, distance and time of staying at the central region among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the time of staying at the original platform quadrant was shortened, the apoptosis rate of hippocampal neurons was increased, and the expression of PKA, p-CREB and BDNF was down-regulated in the other three groups ( P<0.05). Compared with group CPB, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the apoptosis rate of hippocampal neurons was decreased, and the expression of PKA, p-CREB and BDNF was up-regulated in group CS ( P<0.05), and no significant change was found in the indexes mentioned above in group CSH ( P>0.05). Compared with group CS, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the time of staying at the original platform quadrant was shortened, the apoptosis rate of hippocampal neurons was increased, and the expression of PKA, p-CREB and BDNF was down-regulated in group CSH ( P<0.05). Conclusions:Sevoflurane can reduce the apoptosis in hippocampal neurons by activating PKA-CREB signaling pathway, and thus reducing the cognitive impairment induced by CPB in rats.