Effects Of 5-HT_1A Receptor Antagonist On Cognitive Dysfunction In Aged Rats Induced By Sevoflurane

Objective:Based on previous experiments,5-HT_1AA receptor antagonist was administered to lateral ventricle on the basis of sevoflurane induced cognitive dysfunction in elderly rats,and the expression of 5-HT_1AA receptor,cAMP,CaMKII,p-CAMKⅡ,CREB and p-CREB in hippocampal tissues of elderly rats was detected.To test whether 5-HT_1AA receptor antagonist sevoflurane to cognitive dysfunction has a treatment of senile rats,and the hippocampus 5-HT_1AA receptor mediated CaMKII-CREB signaling pathways and cAMP/PKA-after CREB signaling pathways,to clarify 5-HT_1AA receptor antagonist in sevoflurane caused by aging treatment of cognitive dysfunction in rats and its mechanism,provide a new basis for the clinical prevention and treatment of POCD.Methods:40 healthy male aged SD rats aged 18-20 months and weighing about 600⁷50g were selected and divided into 4 groups by random number table method,including10 rats in experimental group C（blank group）（group C,n=10）,10 rats in experimental group 1（group S1,n=10）,10 rats in experimental group 2（group S2,n=10）,and 10 rats in experimental group 3（group S3,n=10）.Experiment 1 set of empty inhaled 50%oxygen gas mixture（2 L/min）and 2%sevoflurane give 0.9%Nacl,4 h back ventricle experiment 2 groups in empty inhaled 50%oxygen mixture（2 L/min）and 2%sevoflurane give 4 h before the left ventricle 5-HT_1AA receptor antagonist,experiment 3 groups in the empty inhaled 50%oxygen mixture（2 L/min）and 2%sevoflurane give 4 h after the left ventricle 5-HT_1Areceptor antagonist,empty control group inhaled 50%oxygen mixture（2/min）4 h.The water maze experiment was carried out in the four experimental groups 6d before and 1d after drug administration,respectively,after the rats were awake,and the time（incubation period）from the rats’entry into the water to finding the platform,the total swimming distance,The Times of crossing the platform and the residence time in the quadrant of the platform were recorded for statistical analysis.At 1d,3d and 7d after administration,the experimental animals were randomly selected and sacrificed,and whole hippocampi on both sides were taken.The expression levels of PKA,CaMKII,p-CAMKⅡ,CREB and p-CREB were detected by real-time PCR and Western blot,and the expression levels of cAMP were detected by Elisa.Results:The results of the water maze experiment showed that,compared with group C,elderly rats in group S1 were given 0.9%Nacl anesthesia in the lateral ventricle under the experimental condition of 2%sevoflurane for 4h,and the escape latency and the total swimming distance were prolonged after awakening.The results of space exploration show that:The Times of crossing the platform are reduced,and the residence time in the quadrant of the platform is reduced（P<0.05）;In contrast,S2,S3and S1 compared the time（incubation period）between water entry and platform finding,and the total swimming distance was shortened.Space exploration experiment:The Times of crossing the platform increased,and the residence time in the quadrant of the platform extended（P<0.05）;Real-time PCR and Western blot data showed that,compared with group C,the expression of 5-HT_1AA receptor in the hippocampal area of experimental group 1 decreased on the first day after treatment,and the expressions of cAMP,PKA,CAMKII,p-CAMKⅡ,CREB and p-CREB were down-regulated（p<0.05）.The expression of 5-HT_1AA receptor in the hippocampus was gradually up-regulated on day 3 and day 7 after administration.On day 7,the expressions of cAMP,PKA,CAMKII,p-CAMKⅡ,CREB and p-CREB were gradually up-regulated,and the expressions were close to group C（p>0.05）.The expression levels of 5-HT_1AA receptors in the hippocampal area increased on day 1 after administration,and the expressions of cAMP,PKA,CAMKII,p-CAMKⅡ,CREB and p-CREB were up-regulated（p<0.05）.The expression of 5-HT_1AA receptor in the hippocampus was gradually up-regulated on day 3 and day 7 after administration.On day 7,the expressions of cAMP,PKA,CAMKII,p-CAMKⅡ,CREB and p-CREB were gradually up-regulated,and the expressions were close to group C（p>0.05）.Conclusion:5-HT_1Areceptor antagonist may have a certain therapeutic effect on sevoflurane induced cognitive dysfunction in elderly rats,which has a certain improvement effect on spatial learning and memory ability of elderly rats.