The Protective Effect Of Dexmedetomidine On Neurotoxicity Of Hippocampal Neuron Cells In Rats Which Was Incubated With Propofol

Objective: With the wide use of general anesthesia, its effect of centraltoxic effect is highlights,especially In the high speed developing period, Generalanesthetics can activate a lot of brain neurons apoptosis. Propofol Is the onepopular of short-acting vein systemic drug,the effect is to activate GABAreceptor and reduce transmission. with its rapid onset, short effectiveness, rapidandno accumulation, Propofol is widely used.However,Research shows thatpropofol as with other drug is not absolute safety, It will lead to nerve toxicity,the Change of the synaptic, damage cognition and memory function.Dexmedetomidine is a new type of α2adrenergic receptor agonist, thecardiovascular protective effect is a clear without sedation and analgesia. Butthe central nervous system effects and mechanism of action is not clear. Tostudy whether microphones can reduce nerve toxicity the propofol caused,through the cultured hippocampal neurons in the experiment.Methods: Sprague Dawley rats on16~18d of pregnancy were sacrificedand fetal rats were taken out form abdominal cavity. The hippocampus of thefetal rats were separated and hippocampal neuron cells were seeded in culture plates for8d. NeuN monoclonal antibody was used to identify whetherhippocampal neuron cells were successful acquired by immunohistochemistrymethod. Cells were divided into eight groups (n=6). The cells in the controlgroup (group C) were incubated with no drugs while the cells in the propofolgroup (group P) were incubated with100μmol/L propofol for3. The cells in thegroup DP1, group DP2, group DP3, group DP4, group DP5or group DP6wereincubated with0.001μmol/L,0.01μmol/L,0.1μmol/L,1μmol/L,10μmol/L or100μmol/L dexmedetomidine respectively for30min and then100μmol/Lpropofol was added to the culture medium for3h. The viability and apoptosisrate of the cells was detected by CCK-8kit and flow cytometry. The mRNAexpression of BDNF, Bcl-2by RT-PCR and the protein expression of p-CREB、BDNF、Bcl-2by Western blot.Results:1.The viability of the cells：The viability of the cells in group P,group DP1, group DP2, group DP3or group DP4was significantly lower thanthat in group C but no significant difference was found among group C, groupDP5and group DP6. The viability of the cells in group DP1, group DP2, groupDP3, group DP4, group DP5or group DP6was significantly higher than that ingroup P.2.The apoptosis rate of the cells: The apoptosis rate of the cells in group P,group DP1, group DP2, group DP3, group DP4or group DP5was significantlylower than that in group C but no significant difference was found among groupC, group DP6. The apoptosis rate of the cells in group DP1, group DP2, groupDP3, group DP4, group DP5or group DP6was significantly higher than that ingroup P.3.The mRNA expression of BDNF：The group P, group DP1, group DP2,group DP3, group DP4or group DP5was significantly lower than that in group C but no significant difference was found among group C, group DP6. Thegroup DP1, group DP2, group DP3, group DP4, group DP5or group DP6wassignificantly higher than that in group P. The mRNA expression of Bcl-2：Thegroup P, group DP1, group DP2, group DP3, group DP4, group DP5or groupDP6was significantly lower than that in group C. The group DP1, group DP2,group DP3, group DP4, group DP5or group DP6was significantly higher thanthat in group P.4.The protein expression of p-CREB、BDNF:The group P, group DP1,group DP2, group DP3, group DP4, group DP5or group DP6was significantlylower than that in group C. The group DP1, group DP2, group DP3, group DP4,group DP5or group DP6was significantly higher than that in group P. Theprotein expression of Bcl-2: The group P, group DP1, group DP2, group DP3,group DP4or group DP5was significantly lower than that in group C but nosignificant difference was found among group C, group DP6. The group DP1,group DP2, group DP3, group DP4, group DP5or group DP6was significantlyhigher than that in group P.Conclusions:1. Propofol can induce apoptosis of hippocampal neuron invitro culture to indicate.2. Dexmedetomidine pretreatment can protect the hippocampal neurons infetal rat on propofol-induced inhibition.3. The neuroprotective effect of dexmedetomidine may through increasethe expression of p-CREB, and then cause the increase of the downstreamBDNF, Bcl-2.