GABA_A受体部分介导丙泊酚在大鼠脊髓水平的抗伤害作用

目的研究丙泊酚在脊髓水平对大鼠伤害性感受的影响及GABAA受体在其中可能的作用。方法Sprague-Daw-ley(SD)♀大鼠随机分组,丙泊酚(Propofol,Pro)和荷包牡丹碱(B icucu lline,B ic)采用鞘内注射(ith)。行为学实验采用热板法和福尔马林实验,分别以舔后爪潜伏时间(Hot-p latelatency,HPL)和疼痛(累计)评分为指标。免疫组化方法观察丙泊酚鞘内给药对福尔马林单侧足底皮下注射诱发的脊髓背角Fos蛋白表达的影响。结果行为学部分:在两种疼痛模型中,鞘内注射丙泊酚(10 g.L-1)产生镇痛作用(P<0.01)。在热板法实验中,鞘内注射丙泊酚(10 g.L-1)产生的镇痛作用在10、20、30和40 min时间点可被鞘内给予Bic(0.01 g.L-1)分别拮抗81%、55%、81%和97%(均P<0.01)。在福尔马林实验中,鞘内注射丙泊酚(10 g.L-1)减少的福尔马林疼痛评分在30 min时间点可被Bic(0.01 g.L-1)相同部位注射拮抗67%(P<0.01)。免疫组化部分:鞘内注射丙泊酚(10 g.L-1)明显减少福尔马林单侧足底皮下注射引起的大鼠同侧腰段脊髓背角各层Fos免疫反应样神经元(Fos-like immunoreactivity,FLI)阳性细胞数(P<0.01);鞘内注射丙泊酚(10 g.L-1)产生的效应可被鞘内注射Bic(0.01 g.L-1)部分拮抗(P<0.01)。结论鞘内注射丙泊酚在大鼠可产生镇痛作用;GABAA受体部分介导了丙泊酚的以上作用。

Partial mediation of GABAA receptor in the antinociceptive stimulation of propofol at spinal level in rats

Aim To observe the effects of propofol at spinal level on nociceptive response in rats and the possible role of GABA_A receptor.Methods In the praxiology test,Sprague-Dawley(SD) female rats were randomized into groups.Bicuculline and propofol were microinjected into intrathecally(ith).The noxious response was evaluated with hot plate and formalin test.In immunohistochemistry test,Fos-like immunoreactivity(FLI) neurons expressed in spinal dorsal horn(DH) induced by formalin intraplantar injection(sc) of one hindpaw were used as a neuroactive marker to observe the effects of propofol on the noxious transmission in DH.Results In hot-plate test,significant analgesia produced by propofol(10 g·L~(-1)) was antagonized about 81%,55%,81% and 97% at 10,20,30 and 40 min by ith bicuculline(0.01 g·L~(-1),P<0.05).In formalin test,the decreased formalin pain scores induced by propofol(10 g·L~(-1)) were antagonized about 67%(P<0.01) by bicuculline(0.01 g·L~(-1)) at 30 min after formalin injection.In immunohistochemistry test,the number of formalin-induced FLI neurons in superficial layer of DH,which induced by formalin intraplantar injection(sc) of one hindpaw in same lateral superficial layer of DH,was significantly depressed by propofol ith. And these effects were significantly antagonized(P<0.01) by bicuculline pretreatment at the same site.Conclusion GABA_A receptor partially mediats propofol-induced analgesia at spinal cord in rats.The effects of propofol on the number of formalin-induced FIL in DH superficial layer are in accordance with the effects in the praxiology test.