Effects Of Propofol On Cell Viability And P38MAPK Activity In Hippocampal Neurons In Vitro

Objective： To investigate the effects of different concentration of propofol on cellviability、apoptosis and p38MAPK activity in hippocampal neurons of fetal rats in vitro.Methods：1. Primary culture of hippocampal neurons, cells cultured for7days were assessed byNSE and Tubulin staining.2. After hippocampal neurons were incubated for7days, the cells were treated withdifferent concentration of propofol alone or with p38inhibitor（SB203580）for24h, MTTwas used to investigate the survival of neurons.3. After hippocampal neurons were incubated for7days, the cells were treated withdifferent concentration of propofol alone or with SB203580for24h, Flow cytometry wasused to investigate the neuronal apopotosis.4. After hippocampal neurons were incubated for7days, the cells were treated withdifferent concentration of propofol for30min, Western-blot analysis was used to observethe expression level of p-p38MAPK and p38MAPK.Results：1. The amount of positive neurons was more than90％of the total number of cells inculture both by NSE and Tubulin staining．2. The results from MTT assay: The survival rate of neurons in DMSO and SB203580group did not vary markedly compared with control group; compared with DMSO group,the cell survival rate was significantly increased in0.5and1μM propofolgroups(P<0.05)and that was significantly lower in10、50、100、150and200μMpropopfol groups in a concentration-dependent manner(P<0.05or P<0.01); After addp38inhibitor, the cell survival rate was still increased in1μM propofolgroup(P<0.05)and that was still lower in10、100and200μM propofol groups in aconcentration-dependent manner(P<0.05or P<0.01); in addition, the survival rate of 100μM propofol with SB203580group was higher than100μM propofol group(P<0.01),the survival rate of200μM propofol with SB203580group was higher than200μMpropofol group(P<0.01), and there was no significantly difference in the cell survival ratebetween other each group and the corresponding concentration added inhibitor group.3. The results from Flow cytometry: compared with DMSO group, the neuronal apoptosisrate was decreased in1μM propofol group(P<0.05)and that was significantly higher in10、100and200μM propopfol groups in a concentration-dependent manner(P<0.05orP<0.01); in addition, the neuronal apoptosis rate of200μM propofol with SB203580group was lower than200μM propofol group(P<0.01), but higher than DMSO groupstill(P<0.01).4. Western blot analysis revealed that the phosphorylation of p38MAPK was highest at30min in200μM propofol group(P<0.01), and compared with DMSO group, thephosphorylation of p38MAPK was significantly higher in10、100and200μM propopfolgroups in a concentration-dependent manner(P<0.05or P<0.01) while that was nosignificantly difference in0.1and1μM propofol groups.Conclusion：1. The effects of propofol on cell viability and apoptosis in hippocampal neurons werebidirectional，subclinical concentration of propofol can inhibit the apoptosis and improvethe survival rate of neurons，while decrease the cell viability through promoting the cellapoptosis in a concentration-dependent manner at high concentration．2. Propofol induces apopotosis of hippocampal neurons by activating p38phosphorylation at high concentration, and that was inhibited by SB203580partly, whilethe expression of p-p38MAPK was no significantly difference in low concentration ofpropofol.