目的观察咪唑安定对氯胺酮诱导大鼠扣带回c-fos基因表达的影响。方法SD大鼠20只,随机分为对照组、咪唑安定组、氯胺酮组和咪唑安定+氯胺酮Ⅰ、Ⅱ组(MKI、Ⅱ组),每组4只。MKⅠ组、Ⅱ组分别腹腔注射眯唑安定2.5、5mg/kg,5min后,腹腔注射100mg/kg氯胺酮。对照组、氯胺酮组、眯唑安定组分别腹腔注射生理盐水、100mg/kg氯胺酮、咪唑安定5mg/kg。2h后,取脑,冰冻切片,进行Fos蛋白免疫组织化学染色。结果氯胺酮组Fos蛋白免疫组织化学阳性神经元(FLIN)明显多于对照组、咪唑安定组(P〈0.01);MKⅠ组、Ⅱ组FLIN均少于氯胺酮组(P〈0.01),而且MKII组明显少于MKI组(P〈0.01)。结论咪唑安定可能通过剂量依赖的抑制氯胺酮诱导的c-fos在扣带回的表达,减轻或消除氯胺酮的精神副作用。
[ Objective ] To investigate the effect of midazolam on ketamine-induced c-fos expression in cingulated cortex of rats. [ Methods ] 20 SD rats were randomly divided into 5 groups : control group, ketamine group, midazolam group, midazolam + ketamine I and I1 group ( MK I and I1 group). The rats in MK Ⅰ and Ⅱ group were injected intraperitoneally 2.5 mg/kg, 5 mg/kg midazolam, followed by 100 mg/kg ketamine injection 5 minutes later. Rats were administered intraperitoneally 0.9% saline, 100 mg/kg ketamine or 5 mg/kg midazolam in the control group, ketamine group and mid- azolam group respectively. The brain of rats were removed and sliced under frozen condition. Immunohistochemical technique for Fos-protein was used. [ Results] The number of Fos-like immunoactivity neurons (FUN) in ketamine group was higher than that in the control group and midazolam groups ( P 〈 0.01 ). The number of FUN in MK Ⅰ and Ⅱ group was fewer than that in midazolam group. Furthermore, the number of FUN in MK Ⅱ group was fewer than that in MK Ⅰ group ( P 〈 0.01 ). [ Conclusion ] Midazolam could inhibit ketamine-induced c-fos expression in cingulated cortex of rats in a dose-dependent manner, by which it alleviated or eliminated neuropsychiatric effects of ketamine.