本文選題：基底核　切入點(diǎn)：丙泊酚　出處：《遵義醫(yī)學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:基底核(nucleus basalis,NB)接受來(lái)自下丘腦和腦干促覺(jué)醒神經(jīng)核團(tuán)的神經(jīng)投射,同時(shí)又發(fā)出神經(jīng)纖維投射到大腦皮層,擔(dān)任網(wǎng)狀上行激活系統(tǒng)和皮層中繼核的作用。丙泊酚是臨床最為常用的靜脈麻醉藥,其主要的作用靶點(diǎn)為GABA_A受體。然而NB及其內(nèi)GABA_A受體是否參與調(diào)控丙泊酚麻醉-覺(jué)醒的過(guò)程尚未明確。本實(shí)驗(yàn)通過(guò)損毀NB或NB微注射GABA_A受體激動(dòng)劑或拮抗劑,觀察丙泊酚麻醉大鼠翻正反射消失(loss of righting reflex,LORR)/恢復(fù)時(shí)間(return of righting reflex,RORR)及對(duì)前額葉皮層(frontal cortex,FC)腦電的影響,探討NB及GABA_A受體在丙泊酚麻醉中的作用機(jī)制,為全麻機(jī)制研究提供新思路。方法:健康雄性SD大鼠50只,體重250-350g。本實(shí)驗(yàn)分為兩部分,第一部分為NB損毀實(shí)驗(yàn),第二部分為NB微注射實(shí)驗(yàn)。第一部分:將20只大鼠隨機(jī)分為2組(n=10):(1)對(duì)照組,單側(cè)NB注入1μl磷酸鹽緩沖液;(2)損毀組,單側(cè)NB注入1μl非特異性損毀藥ibotenic acid(10μg/μl),成功建模14天后開始實(shí)驗(yàn)。首先,采用序貫法測(cè)定尾靜脈注射丙泊酚致大鼠LORR的50%有效劑量(50%effective dose,ED50);其次,以50mg/kg/h的劑量尾靜脈持續(xù)泵入丙泊酚測(cè)定大鼠LORR;最后,單次尾靜脈注射12mg/kg的丙泊酚測(cè)定大鼠RORR,同時(shí)記錄大鼠在丙泊酚(50mg/kg/h)麻醉狀態(tài)下的FC腦電活動(dòng)。第二部分:30只大鼠隨機(jī)分為3組:(1)A組(saline組),NB微注射1μl saline;(2)B組(muscimol組),NB微注射1μl muscimol(GABA_A受體激動(dòng)劑,0.5μg/μl);(3)C組(gabazine組),NB微注射1μl gabazine(GABA_A受體拮抗劑,0.2μg/μl),所有大鼠微注射速度均為0.25μl/min。微注射結(jié)束后,尾靜脈持續(xù)泵入丙泊酚(50mg/kg/h)測(cè)定LORR。尾靜脈注射丙泊酚(12mg/kg)致大鼠LORR后,分別觀察微注射saline/muscimol/gabazine,對(duì)RORR的影響。最后,丙泊酚(50mg/kg/h)麻醉下,測(cè)定NB微注射藥物后對(duì)FC腦電活性的變化。結(jié)果:第一部分:與對(duì)照組相比,IBA(ibotenic acid)損毀~44%單側(cè)NB神經(jīng)元(P0.05)。損毀組LORR的劑量-反應(yīng)性曲線輕度左移(P0.05)。單側(cè)損毀NB未影響LORR(P0.05),但顯著延長(zhǎng)RORR(P0.05),同時(shí)明顯增加丙泊酚麻醉(50mg/kg/h)狀態(tài)下前額葉皮層delta波的比率(P0.05)。第二部分:與saline組相比,NB微注射muscimol后延長(zhǎng)RORR(P0.05),增加FC delta波的比率(P0.05),對(duì)LORR和ED50無(wú)明顯影響(P0.05);NB微注射gabazine則縮短RORR(P0.05),降低FC delta波的比率(P0.05),LORR和ED50未發(fā)生明顯改變(P0.05)。結(jié)論:(1)NB腦區(qū)參與調(diào)控丙泊酚麻醉蘇醒過(guò)程,單側(cè)損毀NB增加FC delta波的比率,延長(zhǎng)丙泊酚麻醉蘇醒時(shí)間。(2)丙泊酚調(diào)控大鼠麻醉蘇醒過(guò)程和FC腦電活性,可由NB內(nèi)GABA_A受體介導(dǎo)。
[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.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R614

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