Effects Of Liraglutide On Oxidative Stress And Apoptosis Of Hippocampal Neurons In Epileptic Rats

Objective:In order to investigate the effect of glucagon like peptide-1(GLP-1) analogues –Liraglutide injection on oxidative stress and neuronal apoptosis in hippocampus tissue,of which epilepsy rats kindled by pentylenetetrazo,we made the experiment.Methods:We selected 48 healthy male Sprague Dawley(SD) rats,which were only 8-9 weeks old and 180g-260 g weight, and we divided them into 4 groups by using the random number table method: normal group(Group sham), model group(group PTZ),liraglutide treatment group(group GLP-1), diazepam treatment group(group DZP), 12 rats in each group. The model of chronic epilepsy rats were kindled by pentylenetetrazol(PTZ).The SD rats in group PTZ, group GLP-1 and group DZP were injected with45mg/kg pentylenetetrazol(PTZ) in the intraperitoneal per day at the same time.The rats in group GLP-1 were injected with 0.03mg/kg liraglutide 20 minutes before the daily injection of pentylenetetrazol, while the rats in group PTZ were injected with equal volume normal saline at the same time. Meanwhile,the rats in group DZP were injected with Diazepam 10mg/kg.The injection for different groups above lasted for two weeks.When the last time injection for different groups was administered, we decapitated the rats and detected the SOD activity and MDA content in hippocampal tissue.Also,after HE staining was performed on hippocampal tissue, we observed the changes of the cell morphological in the hippocampal tissue under light microscope.By the way,we tested the expression of Bax and Bcl-2 protein in hippocampal tissue by immunohistochemistry. The count data was described by mean ± standard deviation, and statistical analysis was performed using SPSS19.0 statistical software.Results:1.SOD activity and MDA level in the hippocampus of rats:The activity of SOD: Compared with group sham, the activity of SOD in group PTZ,group GLP-1, group DZP decreased significantly,which has statistical significance(p<0.05). Compared with group PTZ, the SOD activity of group GLP-1 and group DZP increased dramatically, which was statistically significant(p<0.01). However, there was no obvious difference(p>0.05) between group GLP-1 and group DZP.The content of MDA: Compared with the Group sham, the MDA content of group PTZ, group GLP-1,group DZP increased significantly(p<0.01). Compared with PTZ group, the MDA content in group GLP-1, group DZP increased significantly(p<0.01)too. And it was no obviously different between group GLP-1 and group DZP(p>0.05).2.HE staining results:The hippocampal neurons cells in group sham arranged compactly and closely with clear margin, normal nucleus, transparent cytoplasm and few necrotic neurons. On the contrary, the hippocampal neurons cells in group PTZ showed with scattered arrangement, karyopyknosis, red stained cytoplasm, reduced normal cells and large numbers of necrotic neurons. There were few scattered necrotic neurons in the group GLP-1and group DZP.3.The positive cells' expression of anti-apoptotic Bcl-2, pro-apoptotic Bax: The number of positive cells of Bcl-2 and Bax was expressed in a certain basis in group sham.Bcl-2: Compared with group sham, the expression of Bcl-2 in group PTZ, group GLP-1 and group DZP were significantly increased and the difference is statistically significant(p<0.05). Compared with group PTZ, there was a dramatic increase of the number of Bcl-2 positive cells in group GLP-1, group DZP(p<0.05). But it was not obviously statistical significant between group GLP-1 and group DZP(p>0.05).Bax: The expression of Bax in group PTZ, group GLP-1 and group DZP were more significantly increased than group sham, which has the statistically significant difference(p<0.05). When compared with group PTZ, there was a dramatic decrease of the number of Bax positive cells in group GLP-1, group DZP(p<0.05). However, there was no obviously statistical significance(p>0.05) between group GLP-1 and group DZP.Conclusion:1.The model of rats with chronic epilepsy ignited by pentylenetetrazol could simulate the injuries of human hippocampus neurons well.And by protecting the morphology of the hippocampus neuron cells and decrease the cell apoptosis,which suggested that liraglutide have the protective effect on the brain.2.Liraglutide could reduce the apoptosis of rats' hippocampal neurons and it might play a role by reducing oxidative stress.