异丙酚对氯胺酮所致大脑皮质神经元损害保护作用的机制

目的: 观察异丙酚对氯胺酮诱导的 c-fos 基因在大鼠大脑后扣带回皮质区表达的影响, 并探讨异丙酚预防或减轻氯胺酮所致精神症状及神经损害的机制。方法: 雄性 Wistar 大鼠 30 只, 随机分为生理盐水 5 ml 组、氯胺酮 100 mg°kg^-1组、异丙酚 100 mg°kg^-1组、异 丙 酚 50 mg°kg^-1+氯 胺 酮 100 mg°kg^-1组、异 丙 酚 100 mg°kg^-1+氯 胺 酮 mg°kg^-1 组。异丙酚与氯胺酮用药间隔 15 min。所用药物用生理盐水配至 5 ml 经腹腔注射。各组动物于用药后 2 h, 断头处死, 分离脑组织, 用半定量RT-PCR 技术和免疫组织化学方法检测各组 c-fosmRNA与 c-fos 蛋白在大鼠后扣带回皮质区表达的变化。结果: 氯胺酮可明显诱导 c-fos mRNA 与 c-fos蛋白在大鼠后扣带回皮质区的表达;异丙酚自身不能诱导 c-fos mRNA 和 c-fos 蛋白的表达;预先给予异丙酚可显著抑制氯胺酮诱导的 c-fos mRNA 和 c-fos蛋白在这一区域的表达, 且抑制效应成剂量依赖性。结论: 异丙酚可抑制氯胺酮诱导的 c-fos mRNA 与 c-fos蛋白在大脑后扣带回皮质区的表达, 这可能是其预防或减轻氯胺酮所致精神症状和神经损害的机制之一。

Neuroprotective effects and mechanisms of propofol on neuronal damage induced by ketamine in rat posterior cingulate cortex

AIM: To investigate the effects of propo-fol on ketamine-induced c-fos mRNA and protein expres-sion in the rat posterior cingulate cortex, and to explore the possible mechanisms of using propofol to prevent or treat ketamine-induced psychotomimetic effects and neuro-nal damage.METHODS: Thirty male Wistar rats weigh-ing 250 -300 g were randomly divided into five groups with six animals in each :saline group which received nor-mal saline 5 ml intraperitoneally ip (NS), ketamine 100 group which received ketamine 100 mg°kg^-1 ip (K); propofol 100 group which received propofol 100 mg°kg^-1 ip (P);propofol 50 +ketmaine 100 group which received propofol 50 mg°kg^-1 +ketmaine 100 mg°kg^-1 ip (P 1 K) and propofol 100 +Ketamine 100 group which received propofol 100 mg°kg^-1+Ketamine 100 mg°kg^-1 ip (P 2 K). In group P 1 K and P 2 K, the interval between propofol and ketamine administration was 15 min.Two hours later, the animals were decapitated and brain was removed.c-fos mRNA expression in the posterion cingu-late cortex was detected by semi-quantitative RT-PCR technique, c-fos protein expression in posterior cingulated cortex was determined by immuno-histochemical method. RESULTS: The levels of c-fos mRNA and c-fos protein expression were significantly different among 5 groups. Ketamine induced marked c-fos mRNA and c-fos protein expression in the posterior cingulate cortex.Propofol did not induce c-fos gene expression in this brain region. Propofol significantly inhibited ketamine-induced c-fos mRNA and c-fos protein expression in the posterior cingu-lated cortex in a dose-dependent manner.CONCLUSION: Propofol pretreatment can significantly inhibit ket-amine-induced c-fos mRNA and protein expression in the posterior cingulate cortex. It may be one of mechanisms of inhibition of ketamine-induced psychotomimetic effect and neuronal damage by propofol.