丘脑网状核GABA_A受体参与丙泊酚和异氟醚麻醉机制的作用研究

发布时间：2018-05-15 19:13

本文选题：丘脑网状核 + 丙泊酚　；参考：《遵义医学院》2017年硕士论文

【摘要】：研究背景与目的:近年研究表明丘脑-皮层环路在麻醉及睡眠产生机制中发挥着重要作用,其中丘脑网状核(TRN)是丘脑-皮层环路中重要的抑制性核团,现有研究报道,TRN参与非快动眼(NREM)睡眠,但TRN是否参与全身麻醉过程尚不清楚。故本实验(1)观察TRN对大鼠翻正反射消失时间(LORR)和翻正反射恢复时间(RORR)的影响;(2)通过激活或阻断TRN的GABAA受体,观察麻醉中TRN自身场电位(LFPs)变化及运动皮层(motor cortex,M区)脑电图(EEG)的改变。探讨TRN参与丙泊酚和异氟醚全身麻醉的作用,为全麻机制研究提供新的靶点。方法:本实验(1)行为学:选取健康雄性SD大鼠,随机分为:丙泊酚组(Pro组)、异氟醚组(Iso组)。TRN微注射模型建立后,将建模成功的30只大鼠随机分为Pro组(n=15)、Iso组(n=15)。每组选择自身前后对照法,麻醉前10 min,微注射生理盐水(NS)、GABAAR激动剂(muscimol,0.5μg/μl)、GABAAR拮抗剂(gabazine,0.5μg/μl)。各组首次脑区微注射均以0.25μl/min的速度在TRN脑区注射生理盐水(1μl/side)作为对照,3天后,对同一模型在TRN脑区以0.25μl/min的速度注射muscimol或gabazine(1μl/side);所有大鼠TRN微注射后给予丙泊酚或异氟醚麻醉,观察并记录麻醉后LORR及RORR。新建TRN微注射模型,观察激活或抑制TRN的GABAA受体对麻醉药敏感性的影响。(2)TRN场电位记录:分别记录Pro组/Iso组,TRN微注射(生理盐水、muscimol、gabazine,给药方法同前,n=8)稳定记录微注射前后600s TRN场电位。在相同麻醉深度下,比较TRN微注射给药后的同一频段TRN场电位变化。(3)M区-EEG记录:建立微注射-脑电图记录模型,分别记录Pro组/Iso组麻醉中的M区-EEG,TRN微注射(生理盐水、muscimol、gabazine,给药方法同前,n=8)。在相同的麻醉浓度下,给药前后分别稳定记录600s皮层运动区(M区)脑电图,比较M区-EEG改变。结果:1.TRN微注射GABAAR激动剂缩短丙泊酚组和异氟醚组的LORR(P0.05),且明显延长丙泊酚组和异氟醚组的RORR(P0.05);TRN微注射GABAAR拮抗剂对两组的LORR均没有明显的影响(P0.05),但能缩短两组的RORR(P0.05);2.与对照组相比,TRN微注射GABAAR激动剂使丙泊酚和异氟醚的药物浓度曲线均左移,而GABAAR拮抗剂则无明显改变。3.丙泊酚麻醉下,TRN微注射GABAAR激动剂,明显降低TRN的LFPsδ波比率,增加θ波、α波的比率(P0.05),而其余频段比率无明显变化;微注射GABAAR激动剂增加M区δ波和θ波比率,降低α波和γ波比率(P0.05)。而GABAAR拮抗剂使TRN的LFPsδ波的比率明显增加,α波、β波频段的比率则减少(P0.05);M区的δ波和θ波比率降低,α波(8-12 Hz)和γ波(25-60 Hz)比率(P0.05)升高。4.异氟醚麻醉中,TRN微注射GABAAR激动剂,TRN的LFPsδ波比率减少,减少θ波的比率减少(P0.05);M区δ波比率增加,而α波的比率则明显减少,(P0.05)。微注射GABAAR拮抗剂后,TRN的LFPs的δ波比率降低、θ波频段的比率增加(P0.05);M区δ波、α波及γ波的比率减少,β波的比率则明显增加(P0.05)。结论:1.TRN参与丙泊酚和异氟醚麻醉诱导和苏醒;2.TRN的GABAA受体参与丙泊酚和异氟醚麻醉的调控。
[Abstract]:Research background and purpose: recent studies have shown that thalamic cortical loops play an important role in the mechanism of anesthesia and sleep production. Thalamus reticular nucleus (TRN) is an important inhibitory nucleus in the thalamic cortical loop. The present study has reported that TRN is involved in non fast eye (NREM) sleep sleep, but it is not clear whether TRN is involved in general anesthesia. The experiment (1) observed the effect of TRN on the disappearing time (LORR) and the recovery time (RORR) of the rats. (2) by activating or blocking the GABAA receptor of TRN, the changes of the TRN self field potential (LFPs) and the electrocortex (EEG) of the motor cortex (motor cortex, M region) were observed. The study of the participation of TRN in general anesthesia with propofol and isoflurane was discussed. To provide new targets for the study of general anesthesia mechanism. Methods: this experiment (1) behavior: selected healthy male SD rats, randomly divided into the propofol group (group Pro), the.TRN microinjection model of isoflurane group (group Iso) was established, and the successful 30 rats were randomly divided into Pro group (n=15), Iso group (n=15). Each group selected itself before and after the control method, 10 min before anesthesia. Microinjection of physiological saline (NS), GABAAR agonist (muscimol, 0.5 mu g/ Mu L), GABAAR antagonist (gabazine, 0.5 u g/ Mu L). The first brain region microinjection was injected with physiological saline (1 micron) at the rate of 0.25 mu l/min as control. 3 days later, the same model was injected at the speed of 0.25 mu (1 mu) at the rate of 0.25 mu (1 mu). De); all rats were given anaesthesia with propofol or isoflurane after microinjection of TRN. Observe and record the new TRN microinjection model of LORR and RORR. after anesthesia, and observe the effect of GABAA receptor on the sensitivity of TRN. (2) TRN field potential record: Pro group /Iso group, TRN microinjection (physiological saline, muscimol, administration, administration method) 600s TRN field potential before and after microinjection at the same time. Under the same depth of anesthesia, the TRN field potential changes of the same frequency band after the TRN microinjection were compared. (3) -EEG record in M region: a microinjection electroencephalogram recording model was established to record M region -EEG in group Pro /Iso group anesthesia, and TRN microinjection was given to the prescription. Before and after the same time, n=8). At the same anesthesia concentration, the electroencephalogram of 600s cortex (M area) was recorded steadily before and after the administration, and the -EEG changes in the M region were compared. Results: 1.TRN microinjection of GABAAR agonists shortened LORR (P0.05) in propofol group and isoflurane group, and obviously extended RORR (P0.05) in the propopool group and isoflurane group; TRN microinjected the antagonist. There was no obvious effect on the LORR of the two groups (P0.05), but it could shorten the RORR (P0.05) of two groups. 2. compared with the control group, TRN microinjection of GABAAR agonists left the drug concentration curve of propofol and isoflurane, while GABAAR antagonists did not significantly change the.3. propofol anesthesia, TRN microinjection GABAAR agonist, significantly reduced TRN LFPs delta wave. Ratio, increase the ratio of theta wave and alpha wave (P0.05), but the ratio of other frequency bands does not change obviously; microinjection of GABAAR agonist increases the ratio of delta and theta in M region, reduces the ratio of alpha wave and gamma wave (P0.05). GABAAR antagonists increase the LFPs delta wave ratio of TRN obviously, the ratio of alpha and beta wave frequency decreases (P0.05), and the ratio of delta and theta in M region is reduced, Bo (8-12 Hz) and gamma wave (25-60 Hz) ratio (P0.05) increased.4. isoflurane anesthesia, TRN microinjection of GABAAR agonist, TRN LFPs delta wave ratio decreased, reducing the ratio of theta wave (P0.05); M region delta wave ratio increased, while the ratio of alpha wave decreased significantly, (P0.05). The ratio increases (P0.05); the ratio of delta wave in M region, the ratio of alpha wave to gamma wave and the ratio of beta wave increase significantly (P0.05). Conclusion: 1.TRN is involved in propofol and isoflurane induction and revival, and 2.TRN GABAA receptor is involved in the control of propofol and isoflurane anesthesia.

【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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