Objective: To investigate the mechanisms responsible for the neuroprotection by cholecystokinin octapeptide against glutamate-induced apoptosis in vitro cultured cortical neurons. Methods: Primary cultured corticaI neurons from SD rats of 0～24 hold were incubated for 8 days. The cultured cells were divided randomly into three groups: control group

glutamate group and CCK group. In the controI group

cells were not treated with glutamate orCCK;Neurons in glutamate group were incubated with 50μmol/Lglutamate for 30 min;In CCK group

CCK-8 was added to the Neurons 24 h prior to incubation with glutamate. After injuried by glutamate

cells in all the groups were incubated with normal medium for 0

6

12

24 h and 48 h. At the five time points

cells were fixed respectively for experiment. Cell viability were determined by the colorimetric MTT assay;The protein expression of Bcl-2

Bax and Caspase-3 were determined by immunocytochemistry techniques. Results:Pretreatment with CCK for 24 h significantly improved glutamate-induced suppression of cell viability. Pretreatment with CCK also completely reversed the suppression of Bcl-2 expression

and significantly inhibited Bax overexpression and Caspase-3 activition induced by glutamate. Conclusion:Theneuroprotective mechanisms of CCK against glutamate-induced apoptosis in cultured cortical neurons may be associated with up-regulation of Bcl-2/Bax ratio and down-regulation of Caspase-3.