一氧化氮對大鼠舌下神經(jīng)核的時相依賴性調(diào)控研究
發(fā)布時間：2018-08-01 16:21
【摘要】：[研究背景] 延髓舌下神經(jīng)核(hypoglossal motor nuclei, HMN)的興奮性改變對舌肌在不同腦時相(如睡眠-醒覺期或藥物引致的麻醉狀態(tài))的活性起決定作用。由于睡眠中舌肌活動的抑制能使上氣道狹窄和阻塞,對阻塞性睡眠呼吸暫停低通氣綜合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)的發(fā)生起重要作用,所以確定對HMN興奮性的神經(jīng)影響因素和OSAHS的發(fā)病機制息息相關(guān)。一氧化氮(nitric oxide, NO)是一種可自由擴散的細胞間信號分子,研究發(fā)現(xiàn)有合成NO的神經(jīng)元投射到HMN。HMN同時也含有可溶性腺苷環(huán)化酶(soluble guanylyl cyclase, sGC),一種主要的NO細胞內(nèi)受體酶。雖然已確定NO可作為中樞神經(jīng)系統(tǒng)幾種神經(jīng)元的調(diào)控因子,但它對HMN體內(nèi)情況下的作用尚未得知。本研究擬驗證體內(nèi)情況下NO作為HMN興奮性神經(jīng)遞質(zhì)的假設。 [目的] 了解NO作為一種神經(jīng)遞質(zhì),在腦的麻醉、清醒、非快動眼(non-rapid eye movement, NREM)和快動眼(rapid eye movement, REM)睡眠等不同時相分別作用于舌下神經(jīng)核,其調(diào)控作用如何以及通過何種通路進行調(diào)控。 [方法] 選用了麻醉和自由活動兩種大鼠模型來觀察NO對HMN的調(diào)控作用。 1、麻醉大鼠模型： 雄性成年wistar大鼠,行氣管切開、獲取膈肌、頦舌肌(genioglossus muscle, GG)肌電、動脈血壓,在HMN插入微透析探針,麻醉情況下分別給予遞增濃度的NO供體、NO清除劑、一氧化氮合成酶(nitric oxide synthase, NOS)抑制劑和可溶性腺苷環(huán)化酶(soluble guanylyl cyclase, sGC)抑制劑,以及持續(xù)濃度的NO供體和sGC抑制劑的混合物,觀測GG及膈肌電活動、動脈血壓和呼吸頻率的變化。 2、自由活動大鼠模型： 手術(shù)埋植電極在大鼠GG、膈肌、頸肌及大腦皮層,并在舌下神經(jīng)核上方埋植探針導管。術(shù)后第6-7天,連接GG、膈肌、頸肌及腦電圖電極,實驗前經(jīng)導管插入探針到HMN。兩組大鼠分別持續(xù)透析NO供體和清除劑,記錄各肌電和腦電信號。經(jīng)數(shù)字化處理后,以腦電圖區(qū)分醒覺、NREM、REM睡眠,評估在不同腦時相時該藥物對GG的影響作用。 [結(jié)果] 一、麻醉大鼠模型： 1、NO供體DEA使大鼠的節(jié)律性GG電活動呈濃度依賴性升高。在高濃度DEA(100mmol·L-1)時緊張性電活動亦出現(xiàn)增強。 2、NO清除劑、NOS抑制劑和sGC抑制劑組大鼠的節(jié)律性GG活動明顯降低并呈濃度依賴性。這三組大鼠所有濃度的藥物對緊張性GG活動都無顯著影響。 3、在HMN給予NO供體和sGC抑制劑的混合物,后者有效地抑制了前者對HMN的興奮作用。 二、自由活動大鼠模型： 1、NO供體作用于舌下神經(jīng)核增加NREM睡眠中GG的緊張性活動,但對清醒和REM睡眠期沒有影響。 2、在NO清除劑組的10只大鼠中,不論在哪個時相(NREM睡眠,REM睡眠和清醒),NO清除劑對GG節(jié)律性和緊張性活動的影響均無統(tǒng)計學意義。 [結(jié)論] 1、NO對舌下神經(jīng)核總的來說存在興奮作用。 2、NO在舌下神經(jīng)核局部產(chǎn)生,通過舌下神經(jīng)元的sGC-cGMP通路起作用。 3、NO對HMN興奮作用的特點依賴于腦的不同時相(也就是說,麻醉、清醒、NREM睡眠、REM睡眠)而有所不同。在麻醉狀態(tài)下,NO增強舌下神經(jīng)核的節(jié)律性活動成分。在自由活動動物中,則可增強NREM睡眠期的緊張性活動。
[Abstract]:[research background]
Excitatory changes in the hypoglossal motor nuclei (HMN) of the medulla oblongata play a decisive role in the activity of the lingual muscles in different brain phases, such as sleep wake or drug induced narcotic state. The inhibition of the movement of the tongue in sleep can narrow and obstruct the upper airway, and the obstructive sleep apnea hypopnea syndrome (obstructiv E sleep apnea-hypopnea syndrome, OSAHS) plays an important role in determining the nerve effects on HMN excitability and the pathogenesis of OSAHS. Nitric oxide (nitric oxide, NO) is a free diffusion intercellular signal molecule. The study found that synthetic NO neurons projecting to HMN.HMN are also soluble. Soluble guanylyl cyclase (sGC), a major NO intracellular receptor enzyme. Although NO has been identified as a regulator of several neurons in the central nervous system, its role in the body of HMN has not been known. This study is to verify the hypothesis that NO is a HMN excitatory neurotransmitter in the body.
[Objective]
To understand how NO acts as a neurotransmitter in brain anesthesia, awake, non fast moving eyes (non-rapid eye movement, NREM) and fast moving eye (rapid eye movement, REM) sleep respectively on the hypoglossal nucleus, and how and through which pathway it is regulated.
[method]
Two models of anaesthesia and free movement were used to observe the regulatory effect of NO on HMN.
1, the rat model of anaesthetized rats:
Male adult Wistar rats were treated with tracheotomy, phrenic muscle, geniclingual muscle (genioglossus muscle, GG) myoelectric, arterial blood pressure, and HMN inserted microdialysis probe. Under anesthesia, the increasing concentration of NO donor, NO scavenger, nitric oxide synthase (nitric oxide synthase, NOS) inhibitor and soluble adenosine cyclase (soluble) The changes of GG and diaphragm electromyographic activity, arterial blood pressure and respiratory rate were observed with a mixture of YL cyclase, sGC inhibitor and a continuous concentration of NO donor and sGC inhibitor.
2, free active rat model:
The electrodes were implanted in GG, diaphragm, neck and cerebral cortex in rats, and the probe catheter was implanted above the hypoglossal nucleus. After 6-7 days, GG, diaphragm, neck muscle and electroencephalogram electrode were connected. The NO donor and scavenger were continuously dialysed into HMN. two rats by catheter insertion probe before the experiment. The electromyography and electroencephalogram were recorded. After the EEG was used to distinguish wakefulness, NREM and REM sleep, the effect of the drug on GG was evaluated at different brain phases.
[results]
1. The model of anesthetized rats:
1. NO donor DEA increased the rhythmic GG electrical activity in a concentration-dependent manner, and increased the tension electrical activity at high concentration of DEA (100 mmol.L-1).
2, the rhythmic GG activity of the NO scavenger, the NOS inhibitor and the sGC inhibitor group was significantly reduced and showed a concentration dependence. All the concentrations of the three groups had no significant effect on the activity of tension GG.
3, a mixture of NO donor and sGC inhibitor was given in HMN, which effectively inhibited the excitatory effect of the former on HMN.
Two, free active rat model:
1, the NO donor acts on the hypoglossal nucleus to increase the tension activity of GG in NREM sleep, but has no effect on wakefulness and REM sleep period.
2, in the 10 rats of the NO scavenger group, no matter which phase (NREM sleep, REM sleep and sober), the effect of NO scavenger on GG rhythmic and tension activity was not statistically significant.
[Conclusion]
1, NO has an excitatory effect on the hypoglossal nucleus.
2, NO is localized in the hypoglossal nucleus and plays a role through the sGC-cGMP pathway in hypoglossal neurons.
3, the characteristics of NO's excitatory effect on HMN depend on different phases of the brain (that is, anesthesia, sobriety, NREM sleep, REM sleep). In anaesthetized state, NO enhances the rhythmic activity of the hypoglossal nucleus. In free active animals, it can enhance the tension in the NREM sleep period.
【學位授予單位】：昆明醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R766.4
本文編號：2158148
[Abstract]:[research background]
Excitatory changes in the hypoglossal motor nuclei (HMN) of the medulla oblongata play a decisive role in the activity of the lingual muscles in different brain phases, such as sleep wake or drug induced narcotic state. The inhibition of the movement of the tongue in sleep can narrow and obstruct the upper airway, and the obstructive sleep apnea hypopnea syndrome (obstructiv E sleep apnea-hypopnea syndrome, OSAHS) plays an important role in determining the nerve effects on HMN excitability and the pathogenesis of OSAHS. Nitric oxide (nitric oxide, NO) is a free diffusion intercellular signal molecule. The study found that synthetic NO neurons projecting to HMN.HMN are also soluble. Soluble guanylyl cyclase (sGC), a major NO intracellular receptor enzyme. Although NO has been identified as a regulator of several neurons in the central nervous system, its role in the body of HMN has not been known. This study is to verify the hypothesis that NO is a HMN excitatory neurotransmitter in the body.
[Objective]
To understand how NO acts as a neurotransmitter in brain anesthesia, awake, non fast moving eyes (non-rapid eye movement, NREM) and fast moving eye (rapid eye movement, REM) sleep respectively on the hypoglossal nucleus, and how and through which pathway it is regulated.
[method]
Two models of anaesthesia and free movement were used to observe the regulatory effect of NO on HMN.
1, the rat model of anaesthetized rats:
Male adult Wistar rats were treated with tracheotomy, phrenic muscle, geniclingual muscle (genioglossus muscle, GG) myoelectric, arterial blood pressure, and HMN inserted microdialysis probe. Under anesthesia, the increasing concentration of NO donor, NO scavenger, nitric oxide synthase (nitric oxide synthase, NOS) inhibitor and soluble adenosine cyclase (soluble) The changes of GG and diaphragm electromyographic activity, arterial blood pressure and respiratory rate were observed with a mixture of YL cyclase, sGC inhibitor and a continuous concentration of NO donor and sGC inhibitor.
2, free active rat model:
The electrodes were implanted in GG, diaphragm, neck and cerebral cortex in rats, and the probe catheter was implanted above the hypoglossal nucleus. After 6-7 days, GG, diaphragm, neck muscle and electroencephalogram electrode were connected. The NO donor and scavenger were continuously dialysed into HMN. two rats by catheter insertion probe before the experiment. The electromyography and electroencephalogram were recorded. After the EEG was used to distinguish wakefulness, NREM and REM sleep, the effect of the drug on GG was evaluated at different brain phases.
[results]
1. The model of anesthetized rats:
1. NO donor DEA increased the rhythmic GG electrical activity in a concentration-dependent manner, and increased the tension electrical activity at high concentration of DEA (100 mmol.L-1).
2, the rhythmic GG activity of the NO scavenger, the NOS inhibitor and the sGC inhibitor group was significantly reduced and showed a concentration dependence. All the concentrations of the three groups had no significant effect on the activity of tension GG.
3, a mixture of NO donor and sGC inhibitor was given in HMN, which effectively inhibited the excitatory effect of the former on HMN.
Two, free active rat model:
1, the NO donor acts on the hypoglossal nucleus to increase the tension activity of GG in NREM sleep, but has no effect on wakefulness and REM sleep period.
2, in the 10 rats of the NO scavenger group, no matter which phase (NREM sleep, REM sleep and sober), the effect of NO scavenger on GG rhythmic and tension activity was not statistically significant.
[Conclusion]
1, NO has an excitatory effect on the hypoglossal nucleus.
2, NO is localized in the hypoglossal nucleus and plays a role through the sGC-cGMP pathway in hypoglossal neurons.
3, the characteristics of NO's excitatory effect on HMN depend on different phases of the brain (that is, anesthesia, sobriety, NREM sleep, REM sleep). In anaesthetized state, NO enhances the rhythmic activity of the hypoglossal nucleus. In free active animals, it can enhance the tension in the NREM sleep period.
【學位授予單位】：昆明醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R766.4
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，本文編號：2158148
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