丙泊酚麻醉影响基底核GABA_A受体调控前额叶皮层脑电活动的机制研究

发布时间：2018-03-04 08:02

本文选题：基底核　切入点：丙泊酚　出处：《遵义医学院》2017年硕士论文　论文类型：学位论文

【摘要】：目的:基底核(nucleus basalis,NB)接受来自下丘脑和脑干促觉醒神经核团的神经投射,同时又发出神经纤维投射到大脑皮层,担任网状上行激活系统和皮层中继核的作用。丙泊酚是临床最为常用的静脉麻醉药,其主要的作用靶点为GABA_A受体。然而NB及其内GABA_A受体是否参与调控丙泊酚麻醉-觉醒的过程尚未明确。本实验通过损毁NB或NB微注射GABA_A受体激动剂或拮抗剂,观察丙泊酚麻醉大鼠翻正反射消失(loss of righting reflex,LORR)/恢复时间(return of righting reflex,RORR)及对前额叶皮层(frontal cortex,FC)脑电的影响,探讨NB及GABA_A受体在丙泊酚麻醉中的作用机制,为全麻机制研究提供新思路。方法:健康雄性SD大鼠50只,体重250-350g。本实验分为两部分,第一部分为NB损毁实验,第二部分为NB微注射实验。第一部分:将20只大鼠随机分为2组(n=10):(1)对照组,单侧NB注入1μl磷酸盐缓冲液;(2)损毁组,单侧NB注入1μl非特异性损毁药ibotenic acid(10μg/μl),成功建模14天后开始实验。首先,采用序贯法测定尾静脉注射丙泊酚致大鼠LORR的50%有效剂量(50%effective dose,ED50);其次,以50mg/kg/h的剂量尾静脉持续泵入丙泊酚测定大鼠LORR;最后,单次尾静脉注射12mg/kg的丙泊酚测定大鼠RORR,同时记录大鼠在丙泊酚(50mg/kg/h)麻醉状态下的FC脑电活动。第二部分:30只大鼠随机分为3组:(1)A组(saline组),NB微注射1μl saline;(2)B组(muscimol组),NB微注射1μl muscimol(GABA_A受体激动剂,0.5μg/μl);(3)C组(gabazine组),NB微注射1μl gabazine(GABA_A受体拮抗剂,0.2μg/μl),所有大鼠微注射速度均为0.25μl/min。微注射结束后,尾静脉持续泵入丙泊酚(50mg/kg/h)测定LORR。尾静脉注射丙泊酚(12mg/kg)致大鼠LORR后,分别观察微注射saline/muscimol/gabazine,对RORR的影响。最后,丙泊酚(50mg/kg/h)麻醉下,测定NB微注射药物后对FC脑电活性的变化。结果:第一部分:与对照组相比,IBA(ibotenic acid)损毁~44%单侧NB神经元(P0.05)。损毁组LORR的剂量-反应性曲线轻度左移(P0.05)。单侧损毁NB未影响LORR(P0.05),但显著延长RORR(P0.05),同时明显增加丙泊酚麻醉(50mg/kg/h)状态下前额叶皮层delta波的比率(P0.05)。第二部分:与saline组相比,NB微注射muscimol后延长RORR(P0.05),增加FC delta波的比率(P0.05),对LORR和ED50无明显影响(P0.05);NB微注射gabazine则缩短RORR(P0.05),降低FC delta波的比率(P0.05),LORR和ED50未发生明显改变(P0.05)。结论:(1)NB脑区参与调控丙泊酚麻醉苏醒过程,单侧损毁NB增加FC delta波的比率,延长丙泊酚麻醉苏醒时间。(2)丙泊酚调控大鼠麻醉苏醒过程和FC脑电活性,可由NB内GABA_A受体介导。
[Abstract]:Objective: the basal nucleus basaliscus (NB) receives nerve projections from the hypothalamus and brainstem arousal nuclei, and at the same time sends out nerve fibers to the cerebral cortex. Acting as a reticular uplink activator and cortical relay nucleus. Propofol is the most commonly used intravenous anesthetic in clinical practice. However, it is not clear whether NB and its GABA_A receptors are involved in the regulation of propofol anaesthesia and arousal. In this study, NB or NB microinjection of GABA_A receptor agonists or antagonists was performed. To observe the effect of the loss of righting reflexus / return of righting reflexr (RORR) and the effect of propofol on the brain electrical activity of prefrontal cortex frontal cortexus in rats, and to explore the mechanism of NB and GABA_A receptor in propofol anesthesia, and to explore the mechanism of the effect of NB and GABA_A receptor on propofol anesthesia. Methods: 50 healthy male Sprague-Dawley rats, weighing 250-350 g, were divided into two parts. The first part was NB damage test. The second part was the NB microinjection experiment. The first part: 20 rats were randomly divided into two groups: the control group (n = 10), the control group (n = 10), and the control group (n = 20) treated with 1 渭 l phosphate buffer solution (n = 2). Unilateral NB was injected with 1 渭 l nonspecific lesion drug ibotenic acid(10 渭 g / 渭 l and the model was established 14 days later. First, the 50% fective doseplate ED50 of rat LORR induced by caudal intravenous injection of propofol was determined by sequential method. A dose of 50 mg / kg / h was used to continuously pump propofol into the caudal vein to determine the LORR in rats. A single caudal injection of 12 mg / kg propofol was used to determine the RORRand the FC EEG activity of rats under propofol 50 mg / kg / h anesthesia was recorded. Part two: 30 rats were randomly divided into 3 groups: 1 渭 l saline group, 1 渭 l muscimol group muscimol group. 1 渭 l muscimol(GABA_A receptor agonist (0.5 渭 g / 渭 L) was microinjected into 1 渭 l gabazine(GABA_A receptor antagonist (0. 2 渭 g / 渭 L) in group C, and the microinjection rate was 0. 25 渭 l / min in all rats. After intravenous injection of propofol 12 mg / kg, the effects of microinjection of Saline / muscimol / Gabazine on RORR were observed respectively. Finally, propofol was anesthetized with 50 mg / kg / kg propofol. The changes of FC EEG activity after NB microinjection were measured. Results: the first part: compared with the control group, 44% ipsilateral NB neurons were damaged. The dose-response curve of LORR in the lesion group shifted slightly to the left (P0.05). The unilateral lesion of NB was not seen. The ratio of prefrontal cortex delta waves in propofol anesthetized with 50 mg / kg / h) was significantly increased (P 0.05). Part 2: compared with saline group, the ratio of RORRP0.05and FC delta waves was prolonged after microinjection of muscimol and increased the ratio of FC delta waves to LORR and ED50. Microinjection of gabazine could shorten the RORRN P0.05U, and decrease the ratio of FC delta wave to the ED50. Conclusion the brain area of 1 NB is involved in the adjustment of propofol anaesthesia and recovery process, and the ratio of FC delta wave to LORR and ED50 does not change significantly in the process of propofol anaesthesia. Ipsilateral NB lesion increased the ratio of FC delta wave and prolonged propofol recovery time. 2) propofol regulated the anaesthesia recovery process and FC EEG activity in rats, which could be mediated by GABA_A receptor in NB.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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