依托咪酯对大鼠内侧前额叶皮层乙酰胆碱含量的影响

The effects of etomidate on the concentration of acetylcholine in media prefrontal cortex of the rat

目的:本实验旨在探讨依托咪酯对活体大鼠内侧前额叶皮层(m PFC)乙酰胆碱(ACh)水平的影响。方法:随机选取102只SD大鼠,以尾静脉给予依托咪酯1.0 mg/kg作为起始诱导浓度,以0.5 mg/kg递增,直至5 mg/kg。再以10 mg/(kg·h)为基础维持浓度,以10 mg/(kg·h)递增,直至40 mg/(kg·h),再增加其中间值进行观察,分别明确最低有效诱导和维持翻正反射消失(LORR)的剂量。进一步随机选取12只SD大鼠,随机分为生理盐水组和依托咪酯组。采用微透析技术,在线收集大鼠m PFC给药前后透析液,并自动注射到高效液相色谱仪中以测定ACh浓度。结果:依托咪酯诱导大鼠LORR的最低有效诱导和维持剂量为3.5 mg/kg和32mg/(kg·h)。生理盐水组:组内各个时期ACh水平无明显差异。依托咪酯组:依托咪酯致大鼠意识消失后,m PFC细胞外液ACh水平明显降低(P<0.01);停止输注依托咪酯,细胞外液ACh水平逐渐升高(P<0.01),但未能恢复到基础水平(P<0.01)。结论:尾静脉给予大鼠依托咪酯致意识消失后,可明显降低m PFC细胞外液ACh水平。

Objective:To investigate the effects of etomidate on the acetylcholine(ACh)level in media prefrontal cortex(m PFC)of rats.Methods:102 SD rats were randomly selected as research subjects.Etomidate(1.0 mg/kg)was given to the tail vein as the initial induction concentration,which was then increased by 0.5 mg/kg until the concentration of etomidate became 5 mg/kg.The concentration of 10 mg/(kg·h)was used as the basis,which was then increased by 10 mg/(kg·h)until it became 40 mg/(kg·h).Then the median value of the two concentrations was added to determine the lowest concentration for the effective induction and maintenance dose of loss of righting reflex(LORR).After that,12 SD rats were randomly divided into saline group and etomidate group.Online microdialysis technique was used to collect the dialysates from rats in m PFC before and after etomidate administration.The dialysates were then injected into high performance liquid chromatography(HPLC)automatically to determine the concentration of ACh.Results:The lowest concentration of etomidate for the effective induction and maintenance of LORR in rats was3.5 mg/kg and 32 mg/(kg·h)respectively.For the normal saline group,there was no significant difference in ACh levels in each period.For the etomidate group,the level of ACh in extracellular fluid of m PFC decreased significantly(P<0.01)after the unconsciousness induced by etomidate,and increased gradually(P<0.01)after stopping infusion of etomidate(P<0.01).However,the level of ACh failed to return to the basic level(P<0.01).Conclusion:The level of ACh in the extracellular fluid of m PFC was significantly decreased after administration of etomidate induced unconsciousness in rats.