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Objective To evaluate the role of conventional protein kinase Cγ (cPKCγ)/growthassociated protein-43 (GAP-43) signaling pathway in ketamine-induced apoptosis in hippocampal neurons of developing rats in an in vitro experiment.Methods Primarily cultured hippocampal neurons were seeded in culture plates at a density of 1×10.6 cells/ml and divided into 2 groups (n=10 each) using a random number table:control group (C group) and ketamine group (K group).Group C received no treatment.Ketamine was added with the final concentration of 300 μmol/L in group K.At 12 h of culture or incubation,the apoptosis in hippocampal neurons was detected by flow cytometry.The apoptotic rate was calculated.The expression of cPKCγ,GAP-43 and phosphorylated GAP-43 in hippocampal neurons was measured by Western blot.Results Compared with group C,the apoptotic rates of hippocampal neurons were significantly increased,and the expression of cPKCγ,GAP-43 and phosphorylated GAP-43 was down-regulated in group K (P<0.01).Conclusion The mechanism by which ketamine induces apoptosis in hippocampal neurons of developing rats may be related to inhibition of cPKCγ/GAP-43 signaling pathway activation in an in vitro experiment.
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Objective To evaluate the role of Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway in propofol-induced neuroapoptosis in the hippocampus of newborn rats.Methods Experiment Ⅰ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1×106 cells/ml and divided into 2 groups (n=6 each) using a random number table:solvent control group (C group) and propofol group (P group).Propofol was added with the final concentration of 60 μg/ml in group P.Dimethyl sulfoxide was added with the final concentration of 0.04％ in group C.The expression of RhoA and ROCK2 in hippocampal neurons was measured by Western blot at 24 h of incubation.Experiment Ⅱ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1 × 106 cells/ml and divided into 3 groups (n =6 each) using a random number table:solvent control group (C group),propofol group (P group) and propofol plus specific RhoA/ROCK2 signaling pathway blocker Y27632 group (P+Y group).Propofol was added with the final concentration of 60 μg/ml in group P.Propofol at the final concentration of 60 μg/ml and Y27632 at the final concentration of 10 μmol/L were added in group P+Y.Dimethyl sulfoxide was added with the final concentrauon of 0.04％ in group C.At 24 h of incubation,the neuroapoptosis in hippocampi was detected by flow cytometry,and the expression of activated caspase-3 in hippocampal neurons was measured by Western blot.The apoptotic rate was calculated.Results Experiment Ⅰ Compared with group C,the expression of RhoA and ROCK2 in hippocampal neurons was significantly up-regulated in group P (P＜0.05).Experiment Ⅱ Compared with group C,the apoptotic rate of hippocampal neurons was significantly increased,and the expression of activated caspase-3 was up-regulated in P and P+Y groups (P＜0.05 or 0.01).Compared with group P,the apoptotic rate of hippocampal neurons was significantly decreased,and the expression of activated caspase-3 was down-rcgulatcd in group P + Y (P＜ 0.05).Conclusion Activation of RhoA/ROCK2 signaling pathway is involved in propofol-induced neuroapoptosis in hippocampi of newborn rats.
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Objective To evaluate the relationship between the mechanism underlying propofol-induced inhibition of migration of human breast cancer cells and glyc olysis.Methods Human breast cancer cell line MDA-MB-231 cells were inoculated in 12-well culture plates at a density of 3× 105 cells/well.After being cultured for 24 h,the cells were divided into 2 groups (n=12 each) by using a random number table:control group (group C) and propofol group (group P).Propofol at the final concentration of 5 μg/ml was added to the culture medium in group P,and the equal volume of phosphate buffer solution was added to the culture medium in group C.At 6 h of incubation,the culture media were changed to the common culture media containing no drugs,and the cells were then incubated for another 24 h.The culture media were collected for determination of glucose concentrations (by oxidase mnethod) and lactate concentrations (by chemical colorimetry).Glucose consumption and lactate production were calculated according to glucose and lactate concentrations.Cells were collected,the expression of lactate dehydrogenase A was detected by Western blot,and the migration of cells was determined by cell scratch test.Results Compared with group C,the consumption of glucose and production of lactate were significantly decreased,the expression of lactate dehydrogenase A was down-regulated,and the migration rate was decreased in group P (P＜0.05).Conclusion The mechanism by which propofol inhibits migration of human breast cancer cells may be associated with inhibition of glycolysis.
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Objective To investigate the effects and mechanisms of propofol and dexmedetomidine on neurites and synapses of hippocampal neurons neonatal rats, in vitro. Methods Hippocampal neurons of neonatal Sprague-Dawley rats were cultured 6 days, in vitro and were divided into control group (Group C), solvent of propofol group (Group S), propofol group (Group P), dexmedetomidine group (Group D),propofol and dexmedetomidine group (Group PD), and yohimbine group (Group Y). All groups were cultured for 24 h further. Neuron morphology and the expression of protein were measured. Results After exposing to propofol, we found that the mean total length of neurites of primary cultured hippocampal neurons and synapses and the expression of BDNF, TrkB and CRMP-2 protein were reduced; dexmedetomidine played a protective role. Moreover, yohimbine, partly inhibited neuroprotection of dexmedetomidine. Conclusions Propofol decreases the development of neurites and synapses of hippocampal neurons neonatal rats, in vitro, and dexmedetomidine provides a protective effect on propofol by up-regulating the expression of BDNF, TrkB and CRMP-2. The effect, partly has a concern aboutα2-adrenergic agonist.
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Objective To investigate the effect of different doses of sufentanil combined with dexmedetomidine ( DEX) on hemodynamic and Narcotrend index ( NI) during pediatric anesthesia induction. Methods A total of 45 children with lower abdominal surgery were randomly divided into three groups evenly: sufentanil 0. 1 μg·kg-1+ DEX (S1 group),sufentanil 0. 2 μg·kg-1+DEX (S2 group),and sufentanil 0. 3μg·kg-1+DEX (S3 group). Patients in each group began with intubation at the peak point of administration. Blood pressure,heart rate,perfusion index (PI) and NI were detected at the baseline (t0), delivering DEX 0.5 μg·kg-1·h-1 and sufentanil intravenously for 5 min (t1),delivering sufentanil for 3 min (t2),time of intubation ( t3 ) ,1 min ( t4 ) ,and 5 min ( t5 ) after intubation. The application rate of atropine and propofol was recorded. Patient recovery time and adverse reactions were observed. Results Compared with basicline value at t0 time point, hemodynamic parameters and NI were decreased at t1 and t2 ,while PI was increased in both groups. At t3 ,t4 ,and t5 ,all of the indicators in S1 group were significantly different from those at t0 ,and also significantly different from those in S2 and S3 group. Six patients were treated with propofol in S1 group and four presented with agitation after operation,more than S2 and S3 groups. Three patients were treatment with atropine in S3 group. Conclusion Sufentanil (0. 2 μg·kg-1 ) combined with dexmedetomidine can be used to induce intubation for pediatric anesthesia with stable hemodynamic profile and low incidence of adverse effects.