摘要
背景:多巴胺在维持脑的基本功能(精神、情绪、意识等),控制人对外界环境的反应(运动、知觉、呼吸)等方面具有特殊的重要性,一直是神经科学领域的研究热点。近来研究证实多巴胺在缺氧缺血性脑损伤中扮演重要角色。目的:应用电化学微碳纤电极安培测量法对多巴胺等儿茶酚胺类神经递质的高敏感性和即时性,验证缺血缺氧诱导的儿茶酚胺分泌信号(hypoxia-ischemia induced catecholamine signal,HICS)作为评价脑损伤实时性和稳定性的指标,进一步根据HICS来评价异丙酚的脑保护效应。方法:应用微碳纤电极安培测量法在体定量测量大鼠脑内海马CA1区单胺类物质释放的实时记录系统,首先建立大鼠缺血缺氧模型和HICS模型。然后在HICS模型上静脉注射异丙酚和/或Nomifensine,观察药物对HICS的影响。结果:缺血缺氧性脑损伤可诱导HICS,间隔20-30分钟后,可重复观察到这种信号。大鼠缺氧前静脉注射麻醉剂异丙酚1mg可以显著的降低海马脑区缺氧诱导的多巴胺信号(HISC)升高的幅度(34±19.86 vs 22.19±13.13,n=10,p=0.014)和上升的速率(0.45±0.27 vs 0.33±0.23,n=10,p=0.045);大鼠缺氧前静脉注射可卡因类似物(多巴胺转运体阻断剂)nomifensine 1mg可以显著增加HICS升高的幅度(36.39±21.19 vs 52.96±32.74,n=8,p=0.023)和上升的速率(0.48±0.28 vs 0.78±0.47,n=8,p=0.010);大鼠缺氧前给予nomifensine,然后再静脉注射异丙酚,缺氧前后HICS升高的幅度(51.15±36.11 vs 50.43±35.12,n=4,p=0.490),上升的速率(0.92±0.62 vs 0.88±0.51,n=4,p=0.722)和达峰时间(57.75±13.75 vs 60±23.79,n=4,p=0.789)均没有差异。结论:我们首次实现了在体记录大鼠海马脑区中缺血缺氧诱导的儿茶酚胺分泌信号HICS。这种崭新麻醉状态下的记录缺血缺氧诱发多巴胺信号的方法,信号稳定可靠,在同一动物上可以多次重复,可用于在体研究和评价麻醉条件下脑损伤效果;异丙酚能显著抑制HICS,提示异丙酚除了麻醉功能外,还具有显著的对缺血缺氧性脑损伤的保护作用。本研究为脑缺血缺氧性损伤长期缺少有效的在体实时研究提供了一个创新的在体电化学方法。
Background: Dopamine is an attractive and important neurotransmitter in neurobiological study. It involves multiple functions ranging from movement, cognition, respiration and reinforcement to neurological disorders. Extensive data indicate that dopamine plays an important role in hypoxia-ischemia cerebral injury. Objective: The present study evaluated the effects of propofol on dopamine release in a rat hippocampus model of hypoxia-ischemia injury by using carbon fiber microelectrode (CFE) electrochemical technique in vivo. Methods: First, we utilized CFE electrochemistry technique to quantified the catecholamine release of rat hippocampus CA1 in vivo; second, we set up the model of cerebral hypoxia-ischemic injury; at the end set up the HICS(Hypoxia-ischaemia induced catecholamine signal) model based on the model of HI. Followed by effects of propofol and/or nomifensine on HICS model. Result: HICS could be induced by hypoxia-ischemic cerebral injury in vivo and it could be repeated after 20-30 min. Propofol (1mg iv) pretreatment before hypoxia could significantly inhibit HICS amplitude (34±19.86 vs 22.19±13.13,n=10) (p=0.014) and velocity (0.45±0.27 vs 0.33±0.23, n=10) (p=0.045). Nomifensine (1mg iv)pretreatment before hypoxia could significantly increase HICS amplitude (36.39±21.19 vs 52.96±32.74, n=8) (p=0.023) and accelerate velocity (0.48±0.28 vs 0.78±0.47, n=8) (p=0.010). However,propofol could not reverse the effects of nomifensine on HICS. Conclusion:HICS is an new, stable and reliable signal to estimate neuroprotective effectsin vivo. Our study confirm that propofol can depress HICS significantly,which may suggest that propofol protect cerebral hypoxia-ischemia injury inrat.
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