Propofol促睡眠作用機制研究
發(fā)布時間：2018-10-13 09:29
【摘要】：睡眠和覺醒的發(fā)生及轉(zhuǎn)換被認為是腦內(nèi)神經(jīng)遞質(zhì)和內(nèi)源性睡眠促進物質(zhì)共同作用的結(jié)果,同時受晝夜節(jié)律調(diào)控。動物實驗和臨床證實propofol導致動物或人產(chǎn)生意識喪失和睡眠,低劑量的propofol具有良好的鎮(zhèn)靜作用,但機制尚不清。我們推測propofol麻醉作用可能與睡眠通路相關(guān),可能通過興奮睡眠中樞系統(tǒng),抑制覺醒系統(tǒng)而起作用。本研究采用睡眠覺醒記錄解析的方法和即刻早基因表達和相關(guān)神經(jīng)遞質(zhì)免疫組織化學雙標記技術(shù)揭示propofol對睡眠覺醒時相的調(diào)節(jié)作用和中樞作用靶點及通路,為全面了解propofol作用機制和指導臨床應(yīng)用提供實驗和理論依據(jù)。 方法： SD大鼠隨機分為4組：vehicle (saline)注射組,propofol 1 mg/kg、5 mg/kg和10 mg/kg注射組。肌電(EMG)和腦電(EEG)電極分別植入項肌和腦皮質(zhì)表面以備記錄。術(shù)后恢復(fù)七天,記錄各組EEG和EMG 24 h后22：00分別腹腔注射saline或propofol,解析各組睡眠覺醒時相的改變。藥效作用高峰期1.5小時,處死動物行Fos蛋白標記和調(diào)節(jié)睡眠覺醒重要神經(jīng)遞質(zhì)免疫組化雙標記,觀察propofol的作用導致Fos在睡眠覺醒相關(guān)核團表達活性的變化。 結(jié)果： 1.腹腔注射10 mg/kg propofol抑制大鼠覺醒,EEG顯示為高幅慢波,EMG活動減少,24小時時程為給藥后持續(xù)5小時深慢波睡眠(deep slow wave sleep, SWS2), SWS2平均持續(xù)時間增多,長時程睡眠(960秒)發(fā)生次數(shù)增加,而對其它時相發(fā)生次數(shù)和各時相相互轉(zhuǎn)化次數(shù)無顯著影響,對異相睡眠/快動眼睡眠(paradoxical sleep, PS/rapid eye move sleep, REM sleep)無改變。Propofol 5 mg/kg EEG、EMG以及睡眠圖表現(xiàn)與10 mg/kg相似,但是SWS2時相持續(xù)時間較短,長時程覺醒被破壞,淺慢波睡眠(light slow wave sleep,SWS1)向SWS2以及SWS2向覺醒的轉(zhuǎn)換此時增加。1 mg/kg propofol對睡眠覺醒行為無顯著影響。 2.與生理覺醒組和生理鹽水組相比,10 mg/kg propofol (10 mg/kg)組動物睡眠關(guān)鍵核團腹外側(cè)視前區(qū)(ventrolateral preoptic nucleus, VLPO)區(qū)Fos-IR表達增多,覺醒相關(guān)核團結(jié)節(jié)乳頭體核(tuberomammillary nucleus, TMN)、穹窿周區(qū)(perifornical nucleus, PeF),外側(cè)下丘腦(lateral hypothalamic area, LH)、中腦導水管周圍灰質(zhì)腹側(cè)(ventrolateral periaquiductal gray, vPAG)、中縫核(dorsal raphe nucleus, DRN)Fos-IR均有不同程度的降低,且具有統(tǒng)計學意義,與生理睡眠組動物Fos-IR表達區(qū)域類似。藍斑(locus coeruleus, LC)、中腦被蓋區(qū)(pedunculopontine tegmental bucleus, PPT)以及黑質(zhì)(substantia nigra pars compacta, SNC)Fos-IR各組均無明顯表達。 結(jié)論 1. Propofol劑量依賴性促進SWS2睡眠,縮短睡眠潛伏期,但對PS和SWS1睡眠無明顯影響。 2. Propofol 10 mg/kg引發(fā)SWS2片段的平均持續(xù)時間和長時程發(fā)生次數(shù)增加,但改變其它時相片段發(fā)生次數(shù)及轉(zhuǎn)化次數(shù)與對照組相比無顯著性。提示高劑量propofol引起的睡眠主要是通過增加長時程SWS2時相的持續(xù)時間增加睡眠量。 3. Propofol 5 mg/kg引發(fā)的覺醒,SWS1和SWS2片段發(fā)生次數(shù)以及SWS1向SWS2和SWS2向覺醒轉(zhuǎn)化次數(shù)顯著增加,同時覺醒的平均持續(xù)時間和長時程覺醒發(fā)生次數(shù)減少。提示中劑量可能是通過破壞覺醒的發(fā)生并降低覺醒的持續(xù)時間而增加睡眠量。 4. Propofol通過激活睡眠中樞VLPO神經(jīng)元和抑制覺醒中樞的結(jié)節(jié)乳頭體核、穹窿周區(qū),外側(cè)下丘腦、中腦導水管周圍灰質(zhì)腹側(cè)及中縫核而促進睡眠。
[Abstract]:The occurrence and conversion of sleep and wakefulness is considered to be the result of common action of neurotransmitter and endogenous sleep promoting substance in brain, and is regulated by circadian rhythm. Animal experiments and clinical studies demonstrated that propol resulted in loss of consciousness and sleep in animals or humans, and low doses of propoofol had a good sedative effect, but the mechanism was not clear. We speculate that propool anesthesia may be associated with sleep pathways, possibly by stimulating the central nervous system and inhibiting the wake-up system. The method and the immediate early gene expression of the sleep awakening record and the double labeling technique of the related neurotransmitter are used to disclose the regulating effect and the central action target and the pathway of propol on the sleep awakening, It provides experimental and theoretical basis for comprehensive understanding of propol action mechanism and guiding clinical application. Methods: SD rats were randomly divided into four groups: vehicle injection group, propol 1 mg/ kg, 5mg/ kg and 10m g/ kg injection group. Myoelectric (EMG) and brain electrical (EEG) electrodes were implanted with muscle and brain respectively. The quality surface was prepared for recording. After 7 days of postoperative recovery, the EEG and EMG 24h of each group were recorded, followed by injection of saline or propol, respectively, to analyze the sleep of each group. The effects of propol on sleep-wakefulness-related nuclei were observed. expression of living Results: 1. Intraperitoneal injection of 10 mg/ kg propol inhibited the awakening of rats, EEG was shown as high amplitude slow wave, EMG activity decreased, and after 24 hours, the average duration of SWS2 increased, and the average duration of SWS2 increased. The number of times of onset of sleep (960 seconds) increased, while there was no significant effect on the number of times of phase change and the number of transformation times of each time phase. Sleep and REM sleep were unchanged. Propofol 5 mg/ kg EEG, EMG and sleep patterns were similar to 10 mg/ kg, but the duration of the phase was shorter in SWS2, the long-stroke awakening was destroyed, the transition of light slow wave sleep (SWS1) to SWS2 and SWS2 increased at this time. 1 mg/ kg propo Fol has no significant effect on sleep awakening behavior. Compared with physiological arousal group and physiological saline group, 10 mg/ kg propoofol (10 mg/ kg) group animal sleep key nucleus in the ventral lateral visual anterior region (VLPO) region. Hornical natus, PeF, lateral hypothalamic area (LH), periaqueductal gray system (LH), periaqueductal gray area (vsl), middle-slit nucleus (DRN) and DMR-IR all have a different degree of decrease, and have statistical significance. In physiological sleep group, it is similar to that of the IR-expressing region of the animal. The locus coeruleus (LC), the mesencephalic region of the mesencephalic zone (PPT), and the substeantia nigra pars compacta, S No significant expression was found in each group of NC. Conclusion 1. Propofol dose-dependent promotes SWS2. Sleep, shortened sleep latency, but no significant effect on PS and SWS1 sleep. 2. Propofol 10 mg/ kg induced average duration and duration of SWS2 fragments There was no significant difference between the number of times and the number of conversion times compared with the control group. The resulting sleep was mainly due to increased sleep by increasing the duration of the phase during the long time SWS2. 3. The number of awakening, SWS1 and SWS2 fragments induced by Propofol 5 mg/ kg, and SWS1 to SWS2 and SWS2 The number of awakening transformation was significantly increased, while the average duration of awakening and the number of times of wake-up were decreased. Less. The suggested dose may increase the amount of sleep by destroying the onset of the awakening and decreasing the duration of the awakening. 4. Propoofol activates the central VLPO neuron and inhibits the awakening center.
【學位授予單位】：蘭州大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R338.63
本文編號：2268110
[Abstract]:The occurrence and conversion of sleep and wakefulness is considered to be the result of common action of neurotransmitter and endogenous sleep promoting substance in brain, and is regulated by circadian rhythm. Animal experiments and clinical studies demonstrated that propol resulted in loss of consciousness and sleep in animals or humans, and low doses of propoofol had a good sedative effect, but the mechanism was not clear. We speculate that propool anesthesia may be associated with sleep pathways, possibly by stimulating the central nervous system and inhibiting the wake-up system. The method and the immediate early gene expression of the sleep awakening record and the double labeling technique of the related neurotransmitter are used to disclose the regulating effect and the central action target and the pathway of propol on the sleep awakening, It provides experimental and theoretical basis for comprehensive understanding of propol action mechanism and guiding clinical application. Methods: SD rats were randomly divided into four groups: vehicle injection group, propol 1 mg/ kg, 5mg/ kg and 10m g/ kg injection group. Myoelectric (EMG) and brain electrical (EEG) electrodes were implanted with muscle and brain respectively. The quality surface was prepared for recording. After 7 days of postoperative recovery, the EEG and EMG 24h of each group were recorded, followed by injection of saline or propol, respectively, to analyze the sleep of each group. The effects of propol on sleep-wakefulness-related nuclei were observed. expression of living Results: 1. Intraperitoneal injection of 10 mg/ kg propol inhibited the awakening of rats, EEG was shown as high amplitude slow wave, EMG activity decreased, and after 24 hours, the average duration of SWS2 increased, and the average duration of SWS2 increased. The number of times of onset of sleep (960 seconds) increased, while there was no significant effect on the number of times of phase change and the number of transformation times of each time phase. Sleep and REM sleep were unchanged. Propofol 5 mg/ kg EEG, EMG and sleep patterns were similar to 10 mg/ kg, but the duration of the phase was shorter in SWS2, the long-stroke awakening was destroyed, the transition of light slow wave sleep (SWS1) to SWS2 and SWS2 increased at this time. 1 mg/ kg propo Fol has no significant effect on sleep awakening behavior. Compared with physiological arousal group and physiological saline group, 10 mg/ kg propoofol (10 mg/ kg) group animal sleep key nucleus in the ventral lateral visual anterior region (VLPO) region. Hornical natus, PeF, lateral hypothalamic area (LH), periaqueductal gray system (LH), periaqueductal gray area (vsl), middle-slit nucleus (DRN) and DMR-IR all have a different degree of decrease, and have statistical significance. In physiological sleep group, it is similar to that of the IR-expressing region of the animal. The locus coeruleus (LC), the mesencephalic region of the mesencephalic zone (PPT), and the substeantia nigra pars compacta, S No significant expression was found in each group of NC. Conclusion 1. Propofol dose-dependent promotes SWS2. Sleep, shortened sleep latency, but no significant effect on PS and SWS1 sleep. 2. Propofol 10 mg/ kg induced average duration and duration of SWS2 fragments There was no significant difference between the number of times and the number of conversion times compared with the control group. The resulting sleep was mainly due to increased sleep by increasing the duration of the phase during the long time SWS2. 3. The number of awakening, SWS1 and SWS2 fragments induced by Propofol 5 mg/ kg, and SWS1 to SWS2 and SWS2 The number of awakening transformation was significantly increased, while the average duration of awakening and the number of times of wake-up were decreased. Less. The suggested dose may increase the amount of sleep by destroying the onset of the awakening and decreasing the duration of the awakening. 4. Propoofol activates the central VLPO neuron and inhibits the awakening center.
【學位授予單位】：蘭州大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R338.63
【參考文獻】
相關(guān)期刊論文 前1條
1 湯斌,章功良,王烈成,張瑾,鐘明奎,趙樂章,張景行;腹外側(cè)視前區(qū)GABA能神經(jīng)元對大鼠睡眠-覺醒周期的影響[J];安徽醫(yī)科大學學報;2003年05期
，本文編號：2268110
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