Objective To investigate the role of extracellular signal - regulated protein kinase (ERK)1/2 and nuclear transcription factors (NF - κ B) in the process of bilirubin - induced apoptosis of hippocampal neurons. Methods Hippocampal neurons cultured

in vitro

were divided into treated group (bilirubin)

inhibited group (PD98059 and then bilirubin) and control group (DMSO). Neuronal viability and morphology were tested by modified MTT assay and fluorescent staining with Hoechst33342. The expression of NF

- κ B protein in hippocampal neurons were detected by immunocytochemistry. Results Neuronal viability in treated group [(85.418 ± 1.406)%

]

was significantly decreased compared to that of control group [(99.990 ± 2 . 782)%

P

0 . 01

]

but higher than that in inhibited group [(63.951 ± 1.148)%

P

0 . 01

]

. Moreover

the light density value and positive cell rate of NF - κ B protein in control group were (0.157 ± 0.037) and (0.986 ± 0 . 795)%

respectively

whereas those in inhibited group were (0.249 ± 0.059) and (2.622 ± 1.552)%

both of which were lower than those of treated group [(0.306 ± 0.072) and (6.882 ± 2.626)%

]

respectively (

P

0 . 01). Conclusion ERK/NF - κ B protein signal pathway of hippocampal neuron

in vitro

is activated by bilirubin

and inhibition of ERK/NF - κ B pathway deteriorates neuron apoptosis induced by bilirubin.