本文選題：孤束核　切入點(diǎn)：促食欲素　出處：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：呼吸化學(xué)感受器反射通過(guò)排出CO_2參與調(diào)節(jié)內(nèi)環(huán)境酸堿平衡,是一種重要的穩(wěn)態(tài)調(diào)節(jié)機(jī)制。呼吸頻率和幅度的改變主要由腦干復(fù)雜的神經(jīng)環(huán)路調(diào)控實(shí)現(xiàn)。控制節(jié)律呼吸的神經(jīng)環(huán)路包括從腦橋到低位腦干的一些呈串聯(lián)排列、功能上相互影響的神經(jīng)核團(tuán),其中Botzinger complex和pre-Botzinger complex等是產(chǎn)生呼吸節(jié)律的關(guān)鍵腦區(qū);中樞呼吸化學(xué)感受器和腦橋則為節(jié)律中樞和中樞模式發(fā)生器提供興奮性驅(qū)動(dòng)。孤束核(nucleus tractus solitarii,NTS)是心血管和呼吸系統(tǒng)傳入信息的初級(jí)整合中樞,存在中樞呼吸化學(xué)感受器神經(jīng)元。雖然NTS神經(jīng)元可直接投射到延髓腹側(cè)呼吸組,通過(guò)突觸活動(dòng)影響節(jié)律中樞的活動(dòng),但是,參與投射的神經(jīng)環(huán)路基礎(chǔ)還不明確,投射神經(jīng)元的生物化學(xué)表型也有待揭示。促食欲素(Orexin)是由下丘腦Orexin能神經(jīng)元合成和分泌,參與體內(nèi)許多生理功能的調(diào)節(jié),包括能量代謝、攝食行為、睡眠-覺(jué)醒的交替、獎(jiǎng)賞等。Orexin是中樞性調(diào)控呼吸的重要內(nèi)源性物質(zhì)。研究表明,Pre-Botzinger complex、延髓腹外側(cè)頭端區(qū)、Kolliker-Fuse核、舌下神經(jīng)核、延髓中縫核和斜方體后核的Orexin系統(tǒng)均參與呼吸的頻率和/或幅度的調(diào)節(jié),最終的呼吸改變形式取決于局部神經(jīng)環(huán)路的構(gòu)成、實(shí)驗(yàn)動(dòng)物的狀態(tài)(清醒和睡眠)和生物節(jié)律等。NTS富集Orexin受體(OXR),然而,NTS的Orexin系統(tǒng)是否以及如何參與呼吸運(yùn)動(dòng)的調(diào)節(jié)還未見(jiàn)報(bào)道。目的:觀察NTS的Orexin系統(tǒng)在呼吸調(diào)控中的作用。方法:實(shí)驗(yàn)動(dòng)物分為兩組:OX1R敲低組(注射AAV-U6-OX1R-sh RNA-EGFP)和對(duì)照組(注射AAV-U6-Scrambled-shRNA EGFP)。利用RNA干擾技術(shù),敲低SD大鼠NTS的Ⅰ型Orexin受體(OX1R)。免疫熒光技術(shù)用于檢測(cè)病毒載體的感染效率。qRT-PCR技術(shù)用于測(cè)定OX1R的敲低效率。應(yīng)用無(wú)創(chuàng)體積描計(jì)系統(tǒng)觀察敲低OX1R受體對(duì)清醒大鼠高碳酸性肺通氣反應(yīng)的影響,觀察指標(biāo)為潮氣量(TV)、呼吸頻率(BF)和每分通氣量(MV)等。最后,觀察在NTS注射Orexin對(duì)麻醉大鼠膈神經(jīng)放電、血壓和心率的影響。結(jié)果:1免疫熒光結(jié)果顯示NTS富集OX1R;OX1R-shRNA-EGFP在NTS成功表達(dá)。2 qRT-PCR結(jié)果表明OX1R敲低效率約為15%。3基礎(chǔ)狀態(tài)下(100%O_2,0%CO_2),兩組大鼠的TV和MV無(wú)顯著差異,但敲低組大鼠的BF低于對(duì)照組(P0.0001)。4階梯式增加吸入氣中CO_2濃度(2~8%),兩組大鼠的TV、BF和MV均升高,但OX1R敲低組的TV升高的幅度大于對(duì)照組(P0.05~0.0001),而OX1R敲低組的BF和MV升高的幅度均小于對(duì)照組(P0.05~0.0001)。5 NTS微量注射OrexinA可使麻醉大鼠膈神經(jīng)放電頻率減少(P0.0001),幅度不變,但放電積分值減少(呼吸輸出,P0.0001);同時(shí),收縮壓、舒張壓和平均動(dòng)脈壓降低(P0.001),心率減慢(P0.01)。結(jié)論:清醒狀態(tài)下抑制NTS的Orexin系統(tǒng)可減弱高碳酸性通氣反應(yīng);麻醉狀態(tài)下激活NTS的Orexin系統(tǒng)可抑制中樞性呼吸驅(qū)動(dòng)。因此,孤束核Orexin系統(tǒng)對(duì)呼吸的調(diào)控作用可能呈狀態(tài)依賴性。
[Abstract]:Respiratory chemical receptor reflex is involved in regulating the acid-base balance in the internal environment by excreting CO_2. The changes in respiratory frequency and amplitude are mainly controlled by the complex neural loop of the brain stem. The neural loops that control rhythmic respiration are arranged in series from the pons to the lower brain stem. Botzinger complex and pre-Botzinger complex are the key areas to produce respiratory rhythm. Central respiratory chemosensors and pontine provide excitatory drive for rhythm center and central pattern generator. Nucleus solitarii (NTSs) is the primary integration center of cardiovascular and respiratory afferent information. Although NTS neurons can be directly projected to ventral medulla oblongata and affect the activity of rhythmic center through synaptic activity, the basis of the neural loop involved in the projection is not clear. The biochemical phenotype of projected neurons is also to be revealed. Orexin is synthesized and secreted by Orexin neurons in the hypothalamus, involved in the regulation of many physiological functions in the body, including energy metabolism, feeding behavior, sleep and arousal. Orexin is an important endogenous substance in central respiratory regulation. Studies have shown that Pre-Botzinger complex, Kolliker-Fuse nucleus of ventrolateral medulla oblongata, hypoglossal nucleus, raphe nucleus of medulla oblongata and posterior nucleus obliquus participate in the regulation of respiratory frequency and / or amplitude. The final form of respiratory change depends on the composition of the local neural loop, The state (awake and sleep) and biological rhythm of experimental animals. NTS enriched the Orexin receptor OXRN. However, whether and how the Orexin system of NTS is involved in the regulation of respiratory movement has not been reported. Objective: to observe the Orexin system of NTS in respiratory regulation. Methods: experimental animals were divided into two groups: AAV-U6-OX1R-sh RNA-EGFP group (injected with AAV-U6-OX1R-sh RNA-EGFP) and control group (control group). RNA interference technique was used. Immunofluorescence technique was used to detect the infection efficiency of virus vector. QRT-PCR was used to detect the knockout efficiency of OX1R. The noninvasive volumetric system was used to observe the response of low OX1R receptor to high carbon content in awake rats. Effects of acidic lung ventilation, The indexes of observation were tidal volume, respiratory frequency and ventilation volume, etc. Finally, the phrenic nerve discharges in anesthetized rats were observed by NTS injection of Orexin. Results NTS enriched OX1RX OX1R-shRNA-EGFP was successfully expressed in NTS. The results showed that the OX1R knockdown rate was about 15.3 basic state. The results showed that there was no significant difference in TV and MV between the two groups. However, the BF of the rats in the knockout group was lower than that of the control group (P 0.0001n.4), and the CO_2 concentration in the inhaled gas was increased in step by step. The TV-BF and MV of the rats in the two groups were both increased. However, the amplitude of the increase of TV in the OX1R knockout group was greater than that in the control group (P 0.05 0. 0001), while the increase in BF and MV in the OX1R knockdown group was lower than that in the control group (P 0.05) 0.0001.5 NTS injection of OrexinA could decrease the phrenic nerve discharge frequency of anesthetized rats (P 0. 0001). At the same time, systolic blood pressure, diastolic blood pressure and mean arterial pressure decreased by P 0.001, and the heart rate decreased by P0.010.Conclusion: the Orexin system which suppresses NTS in awake state can weaken the high carbon acid ventilation response. The central respiratory drive can be inhibited by the Orexin system that activates NTS under anesthesia. Therefore, the regulation of respiration by the Orexin system of the nucleus tractus solitarii may be state dependent.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R332.1

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