CAJ | 학술논문

目的咪达唑仑对大鼠背根神经节(DRG)神经元GABAA受体激活电流的影响.方法健康SD大鼠,体重200 ～ 250 g,4周龄,雌雄不拘,分离DRG神经元,采用全细胞膜片钳技术记录GABAA受体激活电流.采用无糖细胞外液进行药物配制.记录咪达唑仑(终浓度3.00 μmol/L,)与不同浓度(终浓度0.03、0.10、1.00、10.00、100.00、1000.00 μmol/L) GABA混合液作用下的GABAA受体激活电流、不同浓度(终浓度0.03、0.10、1.00、3.00、10.00、100.00 μmol/L)咪达唑仑作用下的GABAA受体激活电流、不同浓度(终浓度0.03、0.10、1.00、3.00、10.00、100.00 μmol/L)咪达唑仑与GABA(终浓度100.00 μmol/L)混合液作用下的GABAA受体激活电流和不同咪达唑仑预灌注时间(灌注即刻、20、40、60、120 s)时咪达唑仑(终浓度1.00 μmol/L)与GABA(终浓度100.00 μmol/L)混合液作用下的GABAA受体激活电流.计算咪达唑仑·给药前后电流的增强率.结果对GABA敏感的神经元灌注咪达唑仑均未记录到可检测的膜电流变化;各浓度GABA下,咪达唑仑给药后GABAA受体激活电流均较给药前增强(P＜0.01);各浓度咪达唑仑给药后DRG神经元GABAA受体激活电流均较给药前增强,且随咪达唑仑浓度升高,对DRG神经元GABAA受体激活电流的增强率逐渐升高,咪达唑仑3.00 μmol/L时达峰值(P ＜0.05或0.01);随咪达唑仑预灌流时间延长,DRG神经元GABAA受体激活电流增强率逐渐升高,预灌流40 s时达峰值(β＜0.05或0.01).结论咪达唑仑可增强DRG神经元GABAA受体激活电流,提示咪达唑仑可通过增强GABAA受体活性,从而增强GABA的作用,在脊髓水平产生镇痛作用.
목적 미체서륜대대서배근신경절(DRG)신경원GABAA수체격활전류적영향.방법 건강SD대서,체중200 ～ 250 g,4주령,자웅불구,분리DRG신경원,채용전세포막편겸기술기록GABAA수체격활전류.채용무당세포외액진행약물배제.기록미체서륜(종농도3.00 μmol/L,)여불동농도(종농도0.03、0.10、1.00、10.00、100.00、1000.00 μmol/L) GABA혼합액작용하적GABAA수체격활전류、불동농도(종농도0.03、0.10、1.00、3.00、10.00、100.00 μmol/L)미체서륜작용하적GABAA수체격활전류、불동농도(종농도0.03、0.10、1.00、3.00、10.00、100.00 μmol/L)미체서륜여GABA(종농도100.00 μmol/L)혼합액작용하적GABAA수체격활전류화불동미체서륜예관주시간(관주즉각、20、40、60、120 s)시미체서륜(종농도1.00 μmol/L)여GABA(종농도100.00 μmol/L)혼합액작용하적GABAA수체격활전류.계산미체서륜·급약전후전류적증강솔.결과 대GABA민감적신경원관주미체서륜균미기록도가검측적막전류변화;각농도GABA하,미체서륜급약후GABAA수체격활전류균교급약전증강(P＜0.01);각농도미체서륜급약후DRG신경원GABAA수체격활전류균교급약전증강,차수미체서륜농도승고,대DRG신경원GABAA수체격활전류적증강솔축점승고,미체서륜3.00 μmol/L시체봉치(P ＜0.05혹0.01);수미체서륜예관류시간연장,DRG신경원GABAA수체격활전류증강솔축점승고,예관류40 s시체봉치(β＜0.05혹0.01).결론 미체서륜가증강DRG신경원GABAA수체격활전류,제시미체서륜가통과증강GABAA수체활성,종이증강GABA적작용,재척수수평산생진통작용.
Objective To investigate the effects of midazolam on GABAA receptor-activated currents in isolated dorsal root ganglion (DRG) neurons in rats.Methods Sprague-Dawley rats of both sexes,weighing 200-250 g,aged 4 weeks,were used in the study.The DRG neurons were isolated and GABAA receptor-activated currents were recorded using the whole-cell patch-clamp technique.GABAA receptor-activated currents were recorded after administration of the mixture of midazolam 3.00 μmol/L (final concentration)and the different final concentrations (0.03,0.10,1.00,10.00,100.00 and 1000.00 μmol/L) of GABA,after different concentrations of midazolam (0.03,0.10,1.00,3.00,10.00 and 100.00 μmol/L) was given,after administration of the mixture of different final concentrations(0.03,0.10,1.00,3.00,10.00 and 100.00 μmol/L) of midazolam and GABA 100.00 μmol/L (final concentration),and after administration of the mixture of midazolam 1.00μmol/L (final concentration) and GABA 100.00 μmol/L (final concentration)at the preset time points of perfusion with different concentrations of midazolam (0,20,40,60 and 120 s of perfusion).The enhancement rate of the currents was calculated.Results No change in the membrane currents was found after midazolam was perfused in the neurons sensitive to GABA.GABAA receptor-activated currents were enhanced after administration of the mixture of different concentrations of GABA and midazolam.GABAA receptor-activated currents were enhanced after different concentrations of midazolam were given compared with that before administration,and the enhancement rate of the GABAA receptoractivated currents was gradually increased with the increase in the concentration of midazolam and reached the peak at the concentration of 3.00 μmol/L.The enhancement rate of the GABAA receptor-activated currents was gradually increased with the prolongation of perfusion time and peaked at 40 s of perfusion.Conclusion Midazolam can enhance the GABAA receptor-activated currents in rat dorsal root ganglion neurons,indicating that midazolam increases the role of GABA through increasing the activity of GABAA receptors and has analgesic effect at the spinal cord level.