發(fā)布時間：2018-04-21 06:30

  本文選題：vl-pons + dl-pons��； 參考：《山東大學(xué)》2008年博士論文

【摘要】： 腦橋呼吸調(diào)整中樞由腦橋背外側(cè)(dl-pons)和腦橋腹外側(cè)(vl-pons)兩個結(jié)構(gòu)組成。Dl-pons的主要結(jié)構(gòu)即KF核及臂旁核(PB),vl-pons則主要是指A5區(qū)。Dl-pons和vl-pons之間存在雙向纖維聯(lián)系。眾所周知,腦橋是呼吸調(diào)整中樞所在地,在呼吸節(jié)律的發(fā)起、呼吸時相轉(zhuǎn)換以及呼吸運動協(xié)調(diào)中發(fā)揮重要作用。本課題試圖通過研究腦橋呼吸調(diào)整中樞對呼吸反射的調(diào)節(jié)作用探討腦橋呼吸運動調(diào)控機制。研究分為五部分:第一部分觀察了某些神經(jīng)遞質(zhì)拮抗劑在dl-pons及vl-pons對黑伯反射(肺牽張反射)的影響;第二部分觀察了它們在dl-pons及vl-pons對低氧呼吸反應(yīng)的影響;第三部分應(yīng)用神經(jīng)纖維投射追蹤和免疫組織化學(xué)技術(shù)觀察了dl-pons和vl-pons神經(jīng)元向腦干呼吸反射(低氧呼吸反應(yīng)和黑伯反射)相關(guān)神經(jīng)元的軸突投射;第四部分觀察了小鼠的黑伯反射,并觀察了NMDA受體對小鼠黑伯反射的影響;第五部分觀察了電刺激vl-pons對黑伯反射的調(diào)控及NMDA受體在該過程中的作用。 1、NMDA、GABA_A及AMPA受體拮抗劑在dl-pons及vl-pons對黑伯反射的影響 實驗在35只成年SD大鼠上進(jìn)行,氨基甲酸乙酯腹腔注射麻醉,巴夫龍(pancuronium bromide)肌松,人工通氣。以膈神經(jīng)放電為觀察指標(biāo)。電刺激迷走神經(jīng)模擬黑伯反射。電刺激參數(shù)為:強度20-80μA,頻率80 Hz,波寬0.1 ms,刺激時間60 sec。持續(xù)電刺激迷走神經(jīng)首先出現(xiàn)的是強度依賴性的呼吸暫停、膈神經(jīng)放電停止于呼氣相(Stage-1)。隨著刺激的延續(xù),節(jié)律性膈神經(jīng)放電重新出現(xiàn),呼吸頻率逐漸加快向基線水平恢復(fù)仍然低于基線水平(Stage-2)。刺激停止后出現(xiàn)短暫的呼吸頻率加快并高于刺激前基線水平,該現(xiàn)象主要是由呼氣時間的縮短引起的,稱為刺激后反跳效應(yīng)(PR,Stage-3)。分別在dl-pons及vl-pons微量注射NMDA受體阻斷劑D-2-氨基-5-膦酸基戊酸(D-AP5,10 mM)、GABA受體阻斷劑荷包牡丹堿(bicuculline,BIC,5 mM)及AMPA受體阻斷劑CNQX(6-cyano-7-nitroquinoxaline-2,3-dione,10 mM),注射劑量20-50nl。以注射前黑伯反射為前對照,觀察注射后黑伯反射的改變。結(jié)果發(fā)現(xiàn):(1)在dl-pons微量注射AP5可以增強黑伯反射的呼吸抑制效應(yīng),表現(xiàn)為黑伯反射第一第二階段呼吸頻率下降幅度、呼氣時間延長幅度及吸氣時間縮短幅度均增大;黑伯反射第三階段呼吸頻率仍然低于基線水平,反跳現(xiàn)象消失,該階段吸氣時間增加的幅度明顯增大,上述變化均有顯著性差異。(2)在vl-pons微量注射AP5可以削弱黑伯反射的呼吸抑制效應(yīng),表現(xiàn)為黑伯反射第一第二階段呼吸頻率下降幅度、呼氣時間延長幅度均減小,黑伯反射第三階段呼吸頻率高于基線水平出現(xiàn)反跳現(xiàn)象,但比前對照削弱,上述變化均有顯著性差異。(3)在dl-pons微量注射BIC可以削弱黑伯反射的呼吸抑制效應(yīng),表現(xiàn)為黑伯反射第一階段呼吸頻率下降幅度、呼氣時間延長幅度及吸氣時間縮短幅度均減小,第二階段呼氣時間延長幅度及吸氣時間縮短幅度也減小,第三階段呼氣時間縮短的幅度減小,吸氣時間雖比第二階段有所延長但仍低于基線水平,上述變化均有顯著性差異。第三階段呼吸頻率高于基線水平,出現(xiàn)反跳現(xiàn)象,與前對照相比有所削弱但無顯著性差異。(4)在vl-pons微量注射BIC可以增強黑伯反射的呼吸抑制效應(yīng),表現(xiàn)為黑伯反射第一第二階段呼吸頻率下降幅度、呼氣時間延長幅度及吸氣時間縮短幅度均增大,變化均有顯著性差異;黑伯反射第三階段呼吸頻率高于基線水平,出現(xiàn)反跳現(xiàn)象,與前對照相比有所削弱但無顯著性差異。(5)在dl-pons微量注射AMPA受體阻斷劑CNQX后,黑伯反射三個階段的膈神經(jīng)放電抑制效應(yīng)無明顯變化;(6)在vl-pons微量注射CNQX后,黑伯反射三個階段的膈神經(jīng)放電抑制效應(yīng)也沒有顯著改變。 這些結(jié)果表明存在于dl-pons及vl-pons的由NMDA受體及GABA受體介導(dǎo)的突觸傳遞參與了對黑伯反射強度的調(diào)節(jié),AMPA受體不影響該過程。 2、NMDA、GABA_A及AMPA受體拮抗劑在dl-pons及vl-pons對低氧呼吸反應(yīng)的影響 實驗在35只成年SD大鼠上進(jìn)行。動物制備同前。低氧通氣為8%O_2-92%N_2混合氣體,低氧通氣時間30-50秒。以膈神經(jīng)放電為觀察指標(biāo),分別向dl-pons及vl-pons內(nèi)微量注射NMDA受體阻斷劑D-AP5、GABA受體阻斷劑BIC、AMPA受體阻斷劑CNQX,觀察注射前后低氧通氣時膈神經(jīng)放電的變化。結(jié)果顯示給予大鼠低氧刺激后,膈神經(jīng)放電首先出現(xiàn)頻率升高、吸氣相幅度增大、呼氣時間及吸氣時間均縮短,此謂急性低氧呼吸反應(yīng)。終止低氧恢復(fù)正常通氣后即可出現(xiàn)膈神經(jīng)放電頻率降低并低于低氧刺激前基線水平,此現(xiàn)象稱為低氧后呼吸頻率下降(PHFD)。以微量注射前低氧反應(yīng)為前對照,(1)在dl-pons微量注射D-AP5后,急性低氧反應(yīng)膈神經(jīng)放電無顯著性改變,但PHFD期膈神經(jīng)放電頻率下降幅度減小,即PHFD現(xiàn)象被削弱。(2)在vl-pons微量注射D-AP5后,急性低氧反應(yīng)期及PHFD期膈神經(jīng)放電均無顯著性改變。(3)在dl-pons微量注射BIC后,急性低氧反應(yīng)期膈神經(jīng)放電頻率升高的幅度及呼氣時間縮短的幅度均增大,PHFD期膈神經(jīng)放電無顯著性變化。(4)在vl-pons微量注射BIC后,急性低氧反應(yīng)期膈神經(jīng)放電無顯著性變化,但PHFD期呼吸頻率下降幅度減小。(5)在dl-pons微量注射CNQX后,急性低氧反應(yīng)期膈神經(jīng)放電頻率無明顯變化,但呼氣時間縮短的幅度減小,吸氣時間縮短的幅度增大。PHFD期膈神經(jīng)放電頻率降低的幅度減小。(6)在vl-pons內(nèi)微量注射CNQX后,急性低氧反應(yīng)期吸氣時間縮短的幅度增大,但膈神經(jīng)放電頻率及呼氣時間均無顯著性變化。PHFD期膈神經(jīng)放電頻率降低的幅度減小。 這些結(jié)果表明dl-pons NMDA受體、GABA受體及AMPA受體均參與了對低氧呼吸反應(yīng)的調(diào)節(jié),NMDA受體主要影響低氧后呼吸頻率下降,GABA受體主要影響急性低氧反應(yīng),dl-pons AMPA受體作用則表較復(fù)雜,它既影響急性低氧反應(yīng)又影響低氧后呼吸頻率下降。vl-pons GABA受體及AMPA受體參與了低氧呼吸反應(yīng)的調(diào)節(jié),GABA受體主要影響低氧后呼吸頻率下降,AMPA受體既影響急性低氧反應(yīng)又影響低氧后呼吸頻率下降,NMDA受體沒有參與該反應(yīng)的調(diào)節(jié)。 3、Vl-pons與延髓外周化學(xué)感受性反射及黑伯反射功能相關(guān)神經(jīng)元之間的纖維聯(lián)系 實驗在8只成年SD大鼠上進(jìn)行。腹腔注射苯巴比妥(50 mg/kg)麻醉。在無菌手術(shù)條件下應(yīng)用壓力注射或微電泳方法向dl-pons KF核內(nèi)微量注射Biotin dextran,壓力注射量為20-30 nl(10%)。微電泳注射采用陽極直流電,5μA,15-30分鐘。動物存活10天后給予動物8%的低氧刺激或呼氣末正壓通氣刺激(PEEP)。2-3小時后,腹腔注射氨基甲酸乙酯將動物麻醉,左心室插管灌流、固定,取腦干切片(50μm),用兔抗c-Fos多克隆抗體(一抗)及結(jié)合生物素的羊抗兔IgG(二抗)培育腦片,再用ABC-DAB方法處理腦片,用甲酚紫染色方法染色。結(jié)果發(fā)現(xiàn)發(fā)自dl-pons KF核的纖維投射到已知的延髓呼吸相關(guān)結(jié)構(gòu)。另外單纖維追蹤顯示KF核神經(jīng)元支配多個結(jié)構(gòu)。c-Fos免疫陽性神經(jīng)元主要分布在孤束核內(nèi)側(cè)及腹外側(cè)亞核、延髓腹外側(cè)的外側(cè)網(wǎng)狀核、疑核及其周圍區(qū)域。發(fā)自dl-pons的標(biāo)記纖維末梢與上述c-Fos免疫陽性神經(jīng)元集中存在的區(qū)域重疊,提示dl-pons投射纖維與延髓中參與外周化學(xué)感受器反射及黑伯反射的神經(jīng)元可能存在突觸聯(lián)系。 4、普通野生型及MECP2基因敲除小鼠黑伯反射特點及NMDA受體對其調(diào)節(jié)作用 雷特氏綜合癥(Rett綜合癥)是一種嚴(yán)重影響兒童精神運動發(fā)育的神經(jīng)系統(tǒng)疾病,兒童在6到18個月表現(xiàn)正常,隨后病童會有快速退化及發(fā)育遲緩的現(xiàn)象,并出現(xiàn)陣發(fā)喘氣等呼吸異�，F(xiàn)象,大約26%的Rett綜合癥患者死于呼吸功能紊亂。研究發(fā)現(xiàn)該病可能與methyl-CpG結(jié)合蛋白2(MECP2)基因的突變有關(guān)。我們推測病童所表現(xiàn)出來的呼吸異常癥狀可能與黑伯反射功能異常有關(guān)。本課題第四部分研究了普通野生型(+/+)小鼠及MECP2基因敲除小鼠(+/-)黑伯反射及NMDA受體對該反射的調(diào)控作用。實驗在13只麻醉、肌松、人工通氣的成年小鼠上進(jìn)行。以膈神經(jīng)放電為呼吸觀察指標(biāo),電刺激迷走神經(jīng)中樞端模擬黑伯反射。結(jié)果發(fā)現(xiàn):(1)在+/+小鼠,持續(xù)電刺激迷走神經(jīng)首先出現(xiàn)的是強度依賴性的呼吸暫停、膈神經(jīng)放電停止于呼氣相(Stage-1)。隨著刺激的延續(xù),節(jié)律性膈神經(jīng)放電重新出現(xiàn),呼吸頻率逐漸加快(Stage-2)。在1分鐘刺激將要結(jié)束時,呼氣時間短于迷走刺激前的基線水平,呼吸頻率亦高于基線水平(即“延遲頻率增加”現(xiàn)象)。(2)在8只+/-小鼠上刺激迷走神經(jīng),結(jié)果顯示Stage-1呼吸反應(yīng)與+/+小鼠無明顯區(qū)別。Stage-2呼吸反應(yīng)表現(xiàn)出個體差異。有4只+/-小鼠表現(xiàn)出Stage-2“延遲頻率增加”現(xiàn)象,與+/+小鼠類似。然而在剩余4只+/-小鼠未觀察到該現(xiàn)象。(3)在+/+小鼠和表現(xiàn)出“延遲頻率增加”的+/-小鼠,腹腔注射NMDA受體拮抗劑MK-801后Stage-2呼吸反應(yīng)的“延遲頻率增加”現(xiàn)象均消失。該組實驗顯示Rett綜合癥可能伴隨黑伯反射異常。 5、電刺激dl-pons及向vl-pons內(nèi)微量注射NMDA受體阻斷劑MK-801對黑伯反射的調(diào)控作用 該部分實驗在38只成年Wistar大鼠上進(jìn)行,雌雄不拘。氨基甲酸乙酯腹腔麻醉,用三碘季銨酚肌松,人工通氣,以膈神經(jīng)放電為觀察指標(biāo)。電刺激迷走神經(jīng)模擬黑伯反射。Vl-pons電刺激參數(shù):50-80μA,80 Hz,波寬0.3 ms,刺激時間20 sec,迷走神經(jīng)電刺激參數(shù):20-40μA(1.5×閾值),80 Hz,波寬0.1 msec,刺激時間60 sec。以電刺激vl-pons之前的黑伯反射為前對照,電刺激vl-pons后5 sec內(nèi)再次電刺激迷走神經(jīng)引導(dǎo)出黑伯反射,發(fā)現(xiàn)與前對照相比,黑伯反射的膈神經(jīng)抑制效應(yīng)增強,表現(xiàn)為呼吸頻率下降現(xiàn)象、呼氣時間延長現(xiàn)象、吸氣時間縮短現(xiàn)象更明顯,刺激后反跳現(xiàn)象減弱;以微量注射前黑伯反射為前對照,向vl-pons內(nèi)微量注射MK-801內(nèi)再次電刺激迷走神經(jīng)引導(dǎo)出黑伯反射,發(fā)現(xiàn)與前對照相比,黑伯反射的抑制效應(yīng)減弱,表現(xiàn)為呼吸頻率下降現(xiàn)象、呼氣延長現(xiàn)象、吸氣相縮短現(xiàn)象減弱。 結(jié)果表明vl-pons可以調(diào)制黑伯反射的呼吸抑制作用,并可以調(diào)節(jié)黑伯反射的刺激后反跳現(xiàn)象,并且vl-pons對黑伯反射的調(diào)節(jié)作用是由NMDA受體介導(dǎo)的神經(jīng)遞質(zhì)傳遞介導(dǎo)的。本部分結(jié)果發(fā)表于Adv Exp Med Biol,vol.605,2008。
[Abstract]:The main structure of the pons breathing adjustment center consists of two structures of the lateral lateral pontine (dl-pons) and the lateral ventral pontine (vl-pons). The main structure of the.Dl-pons is the KF nucleus and parobulobial nucleus (PB). Vl-pons mainly refers to the two-way fiber connection between.Dl-pons and vl-pons in the A5 region. It is known that the pontine is the location of the respiratory adjustment center, and the respiratory rhythm is initiated. The study is divided into five parts: the first part of the study is divided into five parts: the first part of the study is to observe some neurotransmitter antagonists in dl-pons and vl-pons to the black eye reflex (lung distraction reaction) The second part observed the effects of dl-pons and vl-pons on hypoxic respiration; the third part observed the axon projection of dl-pons and vl-pons neurons to the brainstem respiratory reflex (hypoxia respiratory response and black Bo reflex) related neurons by nerve fiber projection tracing and immunohistochemical technique; fourth partial views were observed. The effect of NMDA receptor on the mouse reflex was observed, and the fifth part observed the regulation of electric stimulation of vl-pons on the black Bo reflex and the role of NMDA receptor in the process.
1, the effects of NMDA, GABA_A and AMPA receptor antagonists on the dl-pons and vl-pons responses to the black reflex.
The experiment was carried out on 35 adult SD rats with an intraperitoneal injection of ethyl carbamate, pancuronium bromide muscle relaxation and artificial ventilation. The electrical stimulation of the phrenic nerve was used as an observation index. Electric stimulation of the vagus nerve was used to simulate the HB reflex. The electrical stimulation parameters were the intensity of 20-80 Mu, the frequency 80 Hz, the width of the wave width of 0.1 ms, and the stimulation time of 60 sec. sustained electric stimulation. The first appearance of the nerve was the intensity dependent apnea, and the phrenic discharge stopped in the expiratory phase (Stage-1). With the continuation of the stimulation, the rhythmic PHRENIC DISCHARGE reappeared and the respiratory frequency was gradually accelerated to the baseline level still lower than the baseline level (Stage-2). The transient respiratory frequency was accelerated and higher than the stimulus after the prickling stop. The pre baseline level, mainly caused by shortening of the expiratory time, is called PR (Stage-3). NMDA receptor blockers D-2- amino -5- phosphonate (D-AP5,10 mM), GABA receptor blocker (bicuculline, BIC, 5) and receptor blockers are microinjected in dl-pons and vl-pons, respectively. -nitroquinoxaline-2,3-dione, 10 mM), the injection dose of 20-50nl. was used to reflect the change of the black Bo reflex after injection. The results were as follows: (1) the microinjection of AP5 in dl-pons could enhance the respiratory inhibition effect of the HB reflex, showing the decrease of respiratory frequency in the first second stage of the HB reflex and the prolonged exhalation time. The amplitude and the shortening of the inspiratory time were all increased; the third stage of the respiration rate was still lower than the baseline, the phenomenon of the jump disappeared, and the increase in the breathing time increased obviously at this stage, and there was a significant difference in the above changes. (2) the microinjection of vl-pons could reduce the respiratory inhibition effect of the black root reflex, which was manifested by the black root reaction. The respiratory frequency decreased in the first second stages, and the expiratory time was reduced. The third stage of the black Bo reflex was higher than the baseline, but the changes were significantly lower than the previous control. (3) the microinjection of BIC in dl-pons could weaken the respiratory inhibition effect of the black root reflex, which was characterized by black uncle. The respiratory frequency decreased in the first stage, the duration of expiration and the shortening of inspiratory time decreased, the duration of expiration and the shortening of inspiratory time decreased in the second stage, and the shortening of expiratory time decreased in the third stage, while the inhalation time was longer than the second stage, but it was still lower than the baseline level. The third stage of respiratory frequency is higher than the baseline level, and there is a reverse jump phenomenon, which weakens but has no significant difference with the previous picture. (4) the microinjection of vl-pons can enhance the respiratory inhibition effect of the black light reflex, which shows the decrease of the respiratory frequency in the first second stage of the black Bo reflex and the prolongation of the expiratory time. There was a significant difference in the shortening of the degree and the inspiratory time, and there was a significant difference in the change of the respiration rate in the third stage of the black light reflex, which was higher than the baseline level, and there was a reverse jump phenomenon. (5) the inhibitory effect of the phrenic discharge in the three stages of the black Bo reflex after the dl-pons microinjection of AMPA receptor blocker CNQX. There should be no significant change. (6) after vl-pons injection of CNQX, the inhibitory effect of phrenic nerve in three stages of black reflex has not changed significantly.
These results suggest that the synaptic transmission mediated by the NMDA receptor and the GABA receptor in dl-pons and vl-pons participates in the regulation of the intensity of the reflexes, and the AMPA receptor does not affect the process.
2, the effects of NMDA, GABA_A and AMPA receptor antagonists on dl-pons and vl-pons on hypoxic respiratory responses.
The experiment was carried out on 35 adult SD rats. Hypoxic ventilation was 8%O_2-92%N_2 mixed gas and hypoxic ventilation time was 30-50 seconds. With phrenic discharge as the observation index, NMDA receptor blocker D-AP5, GABA receptor blocker BIC, AMPA receptor blocker CNQX, were injected into dl-pons and vl-pons, and the hypoxia was observed before and after injection. The changes in phrenic discharge in gas show that the phrenic discharge is increased first, the amplitude of the phrenic nerve increases, the expiratory time and the expiratory time are shortened, which is called acute hypoxia breathing response. The frequency of phrenic discharge can be reduced and lower than the hypoxic stimulation after the recovery of normal ventilation. Baseline level, this phenomenon is called hypoxic respiratory frequency (PHFD). Before microinjection of microinjection as a pre control, (1) there is no significant change in phrenic discharge in acute hypoxia after microinjection of D-AP5 in dl-pons, but the decrease in frequency of phrenic discharge in PHFD phase decreases, that is, the phenomenon of PHFD is weakened. (2) after vl-pons microinjection of D-AP5, There was no significant change in the acute hypoxic reaction and PHFD PHRENIC DISCHARGE. (3) after dl-pons microinjection of BIC, the amplitude of phrenic discharge and the shortening of the expiratory time increased in the acute hypoxia response period, and there was no significant change in the phrenic discharge at PHFD stage. () after the vl-pons microinjection of BIC, the phrenic deity in the acute hypoxia reaction period was not changed. There was no significant change in discharge, but the decrease of respiratory frequency decreased in PHFD phase. (5) after dl-pons microinjection of CNQX, the frequency of phrenic discharge in acute hypoxia reaction was not significantly changed, but the shortening of expiratory time decreased, and the amplitude of shortening of inhalation time increased in the.PHFD PHRENIC DISCHARGE frequency decrease. (6) in vl-pons After microinjection of CNQX, the shortening of the inhalation time in the acute hypoxia response period increased, but the frequency of phrenic discharge and the expiratory time had no significant changes in the amplitude of the decrease in the frequency of phrenic discharge in the.PHFD phase.
These results suggest that both dl-pons NMDA receptor, GABA receptor and AMPA receptor are involved in the regulation of hypoxia respiration. The NMDA receptor mainly affects the decrease of respiratory rate after hypoxia, and the GABA receptor is mainly affected by the acute hypoxia response. The dl-pons AMPA receptor is more complex. It affects both the acute hypoxia response and the respiratory rate after hypoxia. The reduction of.Vl-pons GABA receptor and AMPA receptor is involved in the regulation of hypoxia respiration. The GABA receptor mainly affects the decrease of respiratory rate after hypoxia. The AMPA receptor affects both the acute hypoxia response and the decrease of respiratory frequency after hypoxia, and the NMDA receptor does not participate in the regulation of the reaction.
3, Vl-pons is related to the fiber connections between the peripheral chemoreceptor reflex and the black reflex function related neurons in the medulla oblongata.
The experiment was carried out on 8 adult SD rats. Intraperitoneal injection of phenobarbital (50 mg/kg) anesthesia. Under the aseptic operation, the dl-pons KF nucleus was injected with Biotin dextran with pressure injection or microelectrophoresis. The pressure injection amount was 20-30 NL (10%). The microelectrophoretic injection was used as anode direct current, 5 mu A, 15-30 minutes. The animals survived for 10 days. After 8% hours of hypoxia stimulation or end expiratory positive pressure ventilation (PEEP).2-3 hours, the intraperitoneal injection of ethyl carbamate was administered to animals, left ventricular intubation, fixation, and brain stem section (50 m). Brain slices were cultured with Rabbit anti c-Fos polyclonal antibody (one anti) and biotin's Sheep anti rabbit IgG (two anti), and then ABC-DAB method was used to deal with brain slices. It was found that the fibers from the dl-pons KF nucleus projected into the known medullary respiratory related structures. In addition, single fiber tracing showed that multiple.C-Fos neurons dominated by KF nucleus neurons were mainly distributed in the medial and ventral subnuclei of the nucleus of the nucleus of the solitary tract, the lateral reticular nucleus of the ventrolateral medulla, the nucleus and the surrounding area. Domain. The labelled fiber terminals from dl-pons overlap with the regions of the above c-Fos immunoreactive neurons, suggesting that there may be synaptic connections between the dl-pons projecting fiber and the neurons involved in the peripheral chemoreceptor reflex and the black Bo reflex in the medulla.
4, the characteristics of black reflex in normal wild type and MECP2 knockout mice and the regulation of NMDA receptors on them.
Rett's syndrome (Rett syndrome) is a nervous system disease that seriously affects children's psychomotor development. Children behave normally in 6 to 18 months, followed by rapid degeneration and developmental retardation, and breathing abnormalities such as intermittent breathing. About 26% of patients with Rett syndrome die from respiratory dysfunction. The disease may be related to the mutation of the methyl-CpG binding protein 2 (MECP2) gene. We speculate that the respiratory abnormalities manifested by the sick child may be related to the abnormality of the abnormality of the reflexes. In the fourth part of this study, the control of the common wild type (+ / +) mice and MECP2 knockout mice (+ / -) and the regulation of the reflex by the NMDA receptor The experiment was conducted on 13 anesthetized, muscular and artificially ventilated adult mice. An electrical stimulation of the phrenic nerve discharge was used as an indicator of respiratory observation and the stimulation of the central terminal of the vagus nerve to simulate the HB reflex. The results were as follows: (1) in a + / + mouse, the first occurrence of the continuous electrical stimulation of the vagus nerve was the intensity dependent apnea, and the phrenic discharge stopped in expiratory phase. (Stage-1). With the continuation of the stimulation, the rhythmic PHRENIC DISCHARGE reappears and the respiratory frequency increases gradually (Stage-2). At the end of the 1 minute stimulus, the expiratory time is shorter than the baseline level before the vagal stimulation, and the respiratory frequency is higher than the baseline level (that is, the "delayed frequency increase"). (2) the vagus nerve is stimulated in 8 + / - mice. The results showed that the Stage-1 respiration reaction and the + / + mice showed no distinct difference in.Stage-2 respiration. 4 + / - mice showed Stage-2 "delayed frequency increase", similar to that of + / + mice. However, in the remaining 4 + / - mice, the phenomenon was not observed. (3) in + / + mice and "delayed frequency increase" + / - mice, abdominal cavity The "delayed frequency increase" of the Stage-2 respiratory response after the injection of the NMDA receptor antagonist MK-801 all disappeared. The experiment showed that the Rett syndrome may be associated with the abnormality of the black abbo reflex.
5, electrical stimulation of dl-pons and microinjection of NMDA receptor blocker MK-801 into vl-pons can regulate the reflex of the brain.
This part of the experiment was carried out on 38 adult Wistar rats. The female and male were not confined to the abdominal anesthesia, with three iodide quaternary ammonium phenol muscle relaxant, artificial ventilation, and phrenic discharge as the observation index. Electric stimulation of the vagus nerve stimulates the electrical stimulation parameters of.Vl-pons: 50-80 mu A, 80 Hz, wave width 0.3 ms, stimulation time 20 sec, electric stimulation of vagus nerve. Parameters: 20-40 mu A (1.5 x threshold), 80 Hz, wave width 0.1 msec, stimulation time 60 sec. to electric stimulation of the black beb reflex before vl-pons as the pre control, electrical stimulation of vl-pons in 5 sec to stimulate the vagus nerve to guide the black root reflex, and found that compared with the previous control, the phrenic inhibition effect of the black Bo reflex was enhanced and the respiratory frequency decreased. Prolonged expiratory time, shortened inhalation time, and decreased rebound after stimulation; microinjection.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R332;R748

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