The Effect Of Q808 On The Cognitive Function And Hippocampus Neuron Apoptosis In Temporal Lobe Epilepsy Rats

Objective:This experiment aims to explore the effect of Q808 on the cognitive function and hippocampus neuron apoptosis in temporal lobe epilepsy(TLE)model rats,and whether it affects the expression of apoptosis-related Bcl-2 and Bax proteins to regulate the apoptosis of neurons and providea reasonablebasis fortheclinical applicationof Q808.Methods:Atotal of 50 healthy male SD rats of clean grade aged 6-8 weeks were selected and were randomly divided as the normal control group(n=10)and experimental groups(n=40).Rats in the normal group were injected with saline intraperitoneally,and rats in the experimental group were induced to establish a lithium chloride-pilocarpine TLE model.30 rats were randomly selected from the 32 successfully modeled rats to be divided into TLE group(n=10),VPA group(n=10),Q808group(n=10).The normal group and the TLE group were administered normal saline(5ml/mouse),once daily;The Q808 group and VPA group were administered antiepileptic drugs Q808(80mg/kg)and sodium valproate(VPA,180 mg/kg),once daily.After 3 weeks,6 rats in each group were randomly selected to test the cognitive ability of each group using the Morris water maze experiment.After 28 days,all rats were decapitated and the hippocampus were removed,and hippocampus were fixed with 4%formaldehyde solution,embedded in paraffin and sectioned,and hippocampus were frozen at-80℃for use.HE staining was used to detect the pathological changes of neurons in the hippocampus of each group of rats;immunohistochemistry and Western Blotting were used to detect the expression and distribution of Bcl-2 protein and Bax protein in the hippocampus of each group of rats.Results1.Morriswatermazeexperimentresults1.1 Place navigation test results:In the PNT experiment,as the number of training days increased,the escape latency of the 4 groups of rats showed a trend of gradually shortening overall.On the 1st day,the 4 groups were compared in pairs,and the results showed no significant difference(P>0.05);on the 2nd day,there was a difference between the TLE group and the Q808 group and the normal group(P<0.05),the VPA group was significantly different from the normal group(P<0.01),and the TLE group and Q808 There was no significant difference between the two groups and the VPA group(P>0.05);on the 3rd and 4th day,there were differences between the TLE group,the Q808 group and the VPA group compared with the normal group(P<0.05),while the TLE group Therewas nosignificantdifferencebetween Q808groupand VPAgroup(P>0.05).1.2 Spatial probe test results:In the SPT experiment,there were differences in the number of times of traversing between the TLE group,Q808 group and VPA group compared with the normal group(P<0.05),while the TLE group,Q808 group and VPA group were paired with each other.There was no significant difference in comparison(P>0.05).The analysis of the trajectories of rats in each group showed that the trajectories of rats in the normal group were the most sparse and relatively concentrated in the target quadrant(quadrant 3).The trajectories of rats in the TLE group,Q808 group and VPA group were all over.Throughout the maze,there was no significant difference in the concentration of the trajectory of the three groups of rats and the concentration of the trajectory in the targetquadrant(quadrant3).2.HE stain results:The hippocampus in the normal group is intact,with a large number of cells,regular and tightly arranged;the hippocampus in the TLE group is incomplete,with a significant decrease in the number of cells,an irregular and disordered morphology,and a significant increase in gaps,and some cells are swollen,The contour disappeared,the cytoplasm was deeply stained,and vacuolated,and the nuclear pyknosis and fragmentation were serious;the above changes in the drug intervention group(VPA group,Q808 group)were significantly reduced compared with the TLE group.3.Immunohistochemical staining results:In terms of Bcl-2~+/Bax~+ratio analysis,compared with the normal group,the Bcl-2~+/Bax~+ratio in the TLE group was significantly reduced(P<0.01),and the Bcl-2~+/Bax~+ratio in the Q808 group was increased(P<0.05),and the VPA group increased significantly(P<0.01);the drug intervention group(Q808 group,VPAgroup)compared with the TLE group,the Bcl-2~+/Bax~+ratioincreasedsignificantly(P<0.01).4.Western blotting results:Interms of Bcl-2/Bax ratio analysis,compared with thenormal group,the Bcl-2/Bax ratio of the TLE group and the drug intervention group(Q808 group,VPAgroup)were significantly lower(P<0.01),and the drug intervention group(Q808)compared with the TLE group,the Bcl-2/Bax ratio was significantly higher than that of the TLE group(P<0.01);the Bcl-2/Bax ratio ofthe VPAgroupwassignificantly higherthanthatofthe Q808 group(P<0.01).Conclusions1.Epilepsycan damagethecognitivefunctionoftemporal lobeepilepsy rats;2.The anti-epileptic drug Q808 has no effect on the cognitive function of temporal lobe epilepsy rats;3.Q808 can improve the pathological changes of hippocampal neurons in temporal lobe epilepsyrats;4.Q808 inhibits the occurrence of hippocampal neuron apoptosis in temporal lobe epilepsy rats by regulating the expression of Bcl-2 and Bax protein.It has a certain neuroprotective effect,but it is not as obvious as sodium valproate.