Abstract: Objective To investigate the effects of cholecystokinin(CCK)-8 on pentylenetetrazole(PTZ)-induced proliferation,apoptosis and activation of glial cells in the mouse hippocampus and its possible mechanisms. Methods First,the cells were randomly divided into control,PTZ-induced,PTZ+CCK-8 low dose,PTZ+CCK-8 middle dose and PTZ+CCK-8 high dose groups.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis and cell cycle.Immunofluorescence was used to detect the expression of activation marker GFAP.ELISA was used to detect the expression levels of GFAP and Cx43.qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of CCK-AR and CCK-BR respectively.Then,with CCK-8 treatment alone as the control,proglumide(a CCK receptor inhibitor)and CCK-8 were used for simultaneous treatment to evaluate the reversing effect of proglumide on the action of CCK-8. Results Compared to the control group,cell proliferation was decreased,apoptosis rate was increased,the proportion of G1 cells was increased,the proportion of G2 cells was decreased,IBA-1 expression was increased,GFAP and Cx43 expression was increased,and mRNA and protein expression of CCK-BR was decreased in the PTZ-induced group.Compared to the PTZ-induced group,cell proliferation was increased,apoptosis rate was decreased,the proportion of G1 cells was decreased,the proportion of G2 cells was decreased,GFAP and Cx43 expression was decreased,and mRNA and protein expression of CCK-BR was increased in the PTZ+CCK-8 group,and all of them were CCK-8 dose-dependent.Compared with the treatment with CCK-8 alone,the combined treatment with proglumide could reverse the effect of CCK-8. Conclusion CCK-8 improves PTZ-induced injury of mouse hippocampal astrocytes through CCK-BR,promotes cell proliferation,reduces apoptosis and inhibits their activation.

Key words: sepsis-associated encephalopathy, cholecystokinin-8, cholecystokinin receptor, astrocyte activation