大鼠延髓腹外侧表面呼吸调节化学感受区的感受机制分析

用免疫组化（ＨＲＰ）、Ｈ＾＋表面透入、核团微量注射、微电泳及损毁等方法探讨了延髓腹侧表面中枢化学感受机制。结果表明它与其浅层核团：斜方体核、外周橄榄腹外侧核（ＬＶＰＯ）、斜方体后核、巨细胞旁外侧核和外侧网状核等有神经结构联系。表面Ｈ＾＋可能被上述核团的突起或胞体感受。非呼吸相关神经元（ＬＶＰＯ）与呼吸相关神经元,同样可能参与中枢化学感受而调节呼吸活动。     

左旋千金藤啶碱D1激动—D2阻滞作用引起伏核双相放电活动的电生理研究

为确定左旋千金藤啶碱（ＳＰＤ）对中脑边缘ＤＡ神经系统的作用特性,本研究采用细胞外记录的电生理学方法,观察微电泳和尾静脉给药对６－ＯＨＤＡ损毁及未损毁大鼠的伏核（ＮＡｃ）单位放电的影响。结果显示：ＳＰＤ累积给药（０．０２－２ｍｇ／ｋｇ,ｉｖ）可诱发ＮＡｃ神经元双相放电特征,即小剂量抑制、大剂量兴奋。预先给予Ｄ２受体拮抗剂ｓｐｅｐｅｒｏｎｅ,ＳＰＤ则仅产生兴奋效应,并被Ｄ１拮抗剂ＳＣＨ－２３３９０所翻     

乙酰胆碱对大鼠头端延髓腹外侧区前交感神经元放电的作用

实验采用细胞外记录和微电泳等电生理方法,研究乙酰胆碱（ＡＣｈ）对氨基甲酸乙酯麻醉的大鼠头端延髓腹外侧区（ＲＶＬＭ）前交感神经元放电频率的影响。在ＲＶＬＭ共记录到３５个前交感神经元,微电泳ＡＣｈ能增加其放电（Ｐ〈０．０５）,并且具有剂量依赖性。其中２２个神经元微电泳Ｍ型胆碱受体阻断剂阿托品（ＡＴＲ）后能明显降低前交感神经元的基础放电（Ｐ〈０．０５）和完全阻断ＡＣｈ引起的神经元兴奋作用;分别向其余７和     

交感神经损毁术对自发性高血压大鼠血压和红细胞Na^＋外流…

本实验研究了皮下注射６－羟多巴胺（６－ＯＨＤＡ）施行交感神经损毁术对成年自发性高血压大鼠（ＳＨＲ）血压和红细胞Ｎａ＾＋外流动力学的影响。结果表明,在幼年期旅行交感神经损毁术的ＳＨＲ血压显著低于未损毁组,同时红细胞Ｎａ泵驱动的Ｎａ＾＋外流最大速率显著下降、Ｎａ＾＋＿Ｋ＾＋外向协同转运系统的单位活性升高。三者均接近ＷＫＹ大鼠的测定值。相反,损毁成年ＳＨＲ交感神经不影响上述两个动力学参数,血压也未见明显     

兔孤束核腹外侧区微量注射谷氨酸钠及甘氨酸对弓状核诱发电位的影响

实验在６６只麻醉、制动,断双侧颈迷走神经和人工通气的家兔上进行。通过微量注射神经元胞体兴奋剂谷氨酸钠和神经元胞体抑制剂甘氨酸,改变孤束核腹外侧区神经元兴奋活动,探讨对下丘脑弓状核诱发电位的影响及其可能的机制和意义。实验结果如下：（１）孤束核腹外侧区微量注射谷氨酸钠,可使膈神经放电显著增加和使弓状核诱发电位Ｐ２及Ｎ２波幅显著降低;而微量注射甘氨酸则使膈神经放电显著减少和使弓状核诱发电位Ｐ２及Ｎ２波幅显著增大。（２）静脉注射纳洛酮对谷氨酸钠引起的膈神经放电兴奋效应无明显影响,但能翻转谷氨酸钠对弓状核诱发电位Ｐ２及Ｎ２波幅的抑制效应。提示：孤束核腹外侧区呼吸神经元的兴奋活动可扩散至弓状核,并对弓状核诱发电位产生影响,此影响可能是由内源性阿片系统参与而实现的。     

大鼠中缝隐核增强dPAG诱导的vPAG的c－Fos表达及对vPAG神经元放电的影响

本实验通过Ｐｏｓ免疫细胞化学、电生理及微量注射法对中缝隐核（ＮＲＯ）的交感抑制作用的相关途径进行探讨。实验在成巴比妥钠或α－氯醛糖和氨基甲酸乙脂麻醉的Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ（ＳＤ）大鼠上进行。同时予以ＮＲＯ,中脑导水管周围灰质背侧部（ｄＰＡＧ）方波脉冲串刺激,诱导中脑和延髓的ｃ－Ｆｏｓ表达。刺激ＮＲＯ过程中,基础血压升高（Ｐ＜０．０５）,刺激ｄＰＡＧ引起的防御性升压反应则减少（Ｐ＜０．０１）;中脑导水管周围灰质腹侧部（ｖＰＡＧ）、巨细胞旁外侧核（ＰＧＬ）的Ｆｏｓ样免疫阳性反应（ＦＬＩ）细胞计数分别为６６．５±８．３和１０．８±１．５（刺激ＮＲＯ＋ｄＰＡＧ组）,较单独刺激ｄＰＡＧ组明显增加,Ｐ值分别小于０．０１和０．００１;单或双脉冲刺激中缝隐核在ｖＰＡＧ可以记录到相关单位,其中８４％为兴奋单位,抑制单位占１６％。双侧ｖＰＡＧ内微量注射利多卡因（每侧２μｇ／０．１μｌ）,基础血压无明显变化,而刺激ＮＲＯ引起的降压反应幅度减小（Ｐ＜０．０１）,提示,延髓腹外侧区（ＶＬＭ）、ＮＲＯ存在不同功能分化的神经元;ＮＲＯ可能有向ｖＰＡＧ的兴奋性投射,此投射可加强ＮＲＯ的交感抑制效应。     

延髓头端腹外侧区血管升压素能机制在应激性高血粘度中的作用

观察延髓头端腹外侧区（ｒＶＬＭ）微量注射血管升压素（ＡＶＰ）能否影响正常大鼠的血压和血粘度,并分析ｒＶＬＭ内ＡＶＰ能机制在清醒大鼠经悬吊加束缚引起应激性升压反应和高血粘度中的影响。结果如下：⑴正常大鼠双侧ｒＶＬＭ微量注射ＡＶＰ（每侧０．５μｇ／０．５μｌ）,可引起血压和血粘度升高;此作用可被事先在同一位置微量注射ＡＶＰ－Ｖ１受体拮抗剂ｄ（ＣＨ２）５「Ｔｙｒ（Ｍｅ）＾２」ＡＶＰ（每侧０．１μｇ／０．     

兔孤束核腹外侧区微量注射保氨酸钠及甘氨酸对弓状核诱发电位的影响

实验在６６只麻醉、制动,断双侧颈迷走神经和人工通气的家兔上进行。通过微量注射神经元胞体兴奋剂谷氨酸钠和神经元胞体抑制剂甘氨酸,改变孤束核腹外侧区神经元兴奋活动,探讨对下丘脑弓状核诱发电位的影响及其可能的机制和意义。实验结果如下：（１）孤束核腹外侧区微量注射谷氨酸钠,可使膈神经放电显著增加和使弓状核诱发电位Ｐ２及Ｎ２波幅显著降低;而微量注射甘氨酸则使膈神经放电显著减少和使弓状核诱发电位Ｐ２及Ｎ２波幅     

头端延髓腹外侧区血管加压素在刺激中脑dPAG区诱发防御性升压反应中的…

雄性Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠,用乌拉坦（７００ｍｇ／ｋｇ）和氯醛糖（３０ｍｇ／ｋｇ）腹腔麻醉。在双侧头端延髓腹外侧区（ｒＶＬＭ区）每侧微量注射血管加压素（ＡＶＰ）（１０ｐｍｏｌ／０．１μｌ）可引起平均动脉压（ＭＢＰ）升高,心率（ＨＲ）变化不明显,每侧微量注射ＡＶＰ的Ｖ１受体拮抗剂ｄ（ＣＨ２）５［Ｔｙｒ（Ｍｅ）＾２］ＡＶＰ（０．１ｎｍｏｌ／０．１μｌ）后ＭＢＰ和ＨＲ无明显变化。若预先在ｒＶＬ     

延髓腹外侧区微量注射L－NNA和SNP对大鼠血压、心率和肾交感神经活动的影响

在麻醉大鼠观察了向延髓腹外侧区微量注射ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（ＬＮＮＡ）和硝普钢（ＳＮＰ）对血压、心率和肾交感神经活动的影响,旨在探讨中枢左旋精氨酸－ＮＯ通路在动脉血压调节中的作用及其机制。实验结果如下：（１）向延髓腹外侧头端区（ＲＶＬＭ）注射Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,肾交感神经活动（ＲＳＮＡ）增强;心率（ＨＲ）减慢,但无统计学意义。ＭＡＰ和ＲＳＮＡ的变化持续３０ｍｉｎ以上;此效应可被预先静注左旋精氨酸所逆转。（２）向ＲＶＬＭ微量注射ＳＮＰ,ＭＡＰ降低,ＲＳＮＡ减弱;但ＨＲ的变化无统计学意义。（３）向延髓腹外侧尾端区（ＣＶＬＭ）注射Ｌ－ＮＮＡ,ＭＡＰ降低,ＨＲ减慢,ＲＳＮＡ减弱。（４）向ＣＶＬＭ微量注射ＳＮＰ,ＭＡＰ升高,ＲＳＮＡ增强,而心率无明显变化。以上结果表明,中枢左旋精氨酸－ＮＯ通路对延髓腹外侧部的神经元活动有调变作用。     

In vivo study on medullary H(+)-sensitive neurons

Using the micro pressure ejection technique, we examined responses of medullary neurons with nonphasic discharges (164 units) to direct application of acidified mock cerebrospinal fluid (CSF, pH 6.85-7.05) in decerebrated spontaneously breathing cats. We found 16 H(+)-sensitive cells; they were excited promptly on application of approximately 500 pl of acidified mock CSF in the vicinity of the neuron under investigation, whereas they were unaffected by microejection of the control mock CSF (pH 7.25-7.60). Of the 16 H(+)-sensitive cells, 10 units were further found to be excited by transcapillary stimulation of the central chemoreceptors by using a method of intravertebral arterial injection of CO2-saturated saline. The discharges increased in a similar time course to that of ventilatory augmentation. Distributions of these 10 specific H(+)-sensitive cells were found in the vicinity of nucleus tractus solitarii as well as deep in the ventrolateral medulla. The present results suggest a possibility that pH-dependent central chemoreceptors, if any, would be located in two distinct medullary regions described in this study.     

延髓中线区在第四脑室注射乙酰胆碱降低肺动脉压和颈动脉压中的作用

本文应用电解损毁和脑内注射药物的方法研究了延髓中线区在第四脑室注射乙酰胆碱(ACh)降低肺动脉压和颈动脉压中的作用。其结果为:1.电解损毁延髓中线区可使ACh引起的肺动脉降压反应和颈动脉降压反应显著减弱。2.在延髓闩水平损毁孤束核对这两种降压反应无影响。3.第四脑室或延髓中线区微量注射5-羟色胺阻断剂赛庚啶或2-溴麦角酰二乙胺均可减弱这两种降压反应。4.第四脑室或延髓中线区微量注射阿片受体阳断剂纳洛酮能部分消除这两种降压反应。这些结结表明:ACh所致的肺动脉降压反应和颈动脉降压反应均与延髓中线区结构有关,而与缓冲神经的投射部位无关。它们可能是通过兴奋延髓中缝核5-羟色胺和内啡呔系统,抑制脊髓交感节前神经元而实现的。     

Identification of a subsurface area in the ventral medulla sensitive to local changes in PCO2.

The exact location of the central respiratory chemoreceptors sensitive to changes in PCO2 has not yet been determined. To avoid the confounding effects of the cerebral circulation, we used the in vitro brain stem-spinal cord of neonatal rats (1-5 days old) to identify areas within 500 microns of the ventral surface of the medulla where changes in PCO2 evoked a sudden increase in the rate of respiratory neural activity. The preparation was superfused with mock cerebrospinal fluid (CSF) while maintained at constant temperature (26 +/- 1 degrees C) and pH (7.34). Respiratory frequency increased linearly with decreases in superfusate pH (r2 = 0.92, P less than 0.001), indicating that the respiratory circuitry for the detection of CO2 and stimulation of breathing was intact in this preparation. The search for central chemoreceptors was performed with a specially designed micropipette that allowed microejection of 2-10 nl of mock CSF equilibrated with different CO2-O2 gas mixtures. The pipette was advanced in 50- to 100-microns steps by use of a microdrive to a maximum depth of 500 microns from the surface of the ventral medulla. Depending on the location of the micropipette, ejection of CO2-acidified mock CSF at depths of 100-350 microns below the ventral surface of the medulla stimulated neural respiratory output. Using this response as an indication of the location of central respiratory chemoreceptors, we found that chemoreceptive elements were located in a column in the ventromedial medulla extending from the hypoglossal rootlets caudally to an area 0.75 mm caudal to VI nerve in the rostral medulla.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central cardiorespiratory effects of glutamate in dogs

Metabolism of certain amino acid neurotransmitters such as glutamate and gamma-aminobutyric acid (GABA) are closely linked in the brain to CO2 fixation and H+ metabolism. Additionally they may also affect central modulation of cardiorespiratory function. Therefore central cardiorespiratory effects of L-glutamate were determined in lightly anesthetized dogs using ventriculocisternal perfusion with artificial cerebrospinal fluid (CSF) (pH 7.25-7.28) containing 30 or 60 mM glutamate at a flow rate of 1.0 ml/min for 20 min followed by perfusion with artificial CSF alone. Tidal volume and minute ventilation increased with 60 mM glutamate, as did respiratory drive. These changes returned to normal with mock CSF perfusion. Glutamate (30 mM) had no significant effect on ventilation. At both concentrations, glutamate significantly increased mean femoral arterial pressure and mean pulmonary arterial pressure, which was accompanied by bradycardia. All these increases rapidly returned to normal with mock CSF perfusion. Cardiac output and pulmonary capillary wedge pressure did not change with glutamate perfusion. The results suggest that glutamate may have a significant central excitatory role in modulation of ventilatory drive as well as of hemodynamic functions.     

氟安定对家兔结合臂旁核区呼吸性单位放电的影响

在36只麻醉、麻痹、切断双侧颈迷走神经及人工呼吸的家兔上,用五管微电极记录结合臂旁核区细胞外放电并微电泳药物离子。在47个吸气性单位(IUs)、18个呼气性单位(EUs)、12个吸-呼跨根性单位(I-EUs)、11个呼-吸跨相性单位(E-IUs)和71个非呼吸性单位(NR-Us)中,微电泳氟安定(Flu)引起阻遏的单位分别占55.3％、94.4％、91.7％、18.1％和60.6％。经统计:Flu抑制IUs和EUs的百分率与抑制I-EUs和E-IUs的百分率有显著差别。GABA-A受体拮抗剂荷包牡丹碱不能阻断Flu对IUs和EUs的阻遏作用,但能阻断Flu对NRUs的抑制作用,阻断率为60％。在20个IUs中,ACh引起兴奋效应的占75％,未见有阻遏效应的;ACh对其它类型呼吸性单位(RUs)则有不同的效应。ACh不能对抗Flu的阻遏效应。ACh对NRUs主要呈兴奋效应。以上结果表明:Flu对结合臂旁核区RUs和NRUs主要起抑制作用,其中抑制EUs和I-EUs的作用较大;而且,Flu抑制RUs和NRUs的递质机制有差异,抑制NRUs可能主要通过内源性GABA系统,而抑制RUs的机制则不提示有该系统参与。ACh对IUs和NRUs主要起兴奋作用。     

Increase in vasopressin concentration and cardiodepressant activity in the blood dialysates after NMDA and hypertonic saline administration.

It has been demonstrated that electric stimulation of the central ends of cut vagus nerves or angiotensin II infusion cause an increase in vasopressin concentration and cardiodepressant activity in the sella turcica venous blood. The present study was an attempt to determine if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into the blood dialysate after osmotic stimulation, and whether excitatory amino acids are involved in this mechanism. The samples of dialysates of venous blood flowing from the sella turcica region and, for comparison, from the femoral vein were collected in anaesthetised rats. The concentration of vasopressin in blood dialysate was determined by radioimmunoassay, and cardiodepressant activity on spontaneously discharging pacemaker tissue of the right auricle of the right heart atrium. Osmotic stimulation or N-methyl-D-aspartic acid infusion caused an increase in cardiodepressant activity and vasopressin concentration in the blood dialysate from the sella turcica and from the femoral vein. A blockade of the excitatory amino acids receptors by specific and non-specific antagonists significantly inhibited the increase in the blood dialysate vasopressin concentration and cardiodepressant activity elicited by an intra-arterial injection of hypertonic saline. These data indicate that excitatory amino acids are involved in the mechanism of increase in blood vasopressin and cardiodepressant factor concentration in response to osmotic stimulation. These results also demonstrate the utility of blood minidialysis for simultaneous monitoring of active substances concentration in the blood.     

中缝大核在臂旁内侧核区注射吗啡所致呼吸抑制效应中的作用

实验在33只浅麻醉、肌肉麻痹、人工呼吸及切断双侧颈迷走神经的家兔上进行。观察中缝大核区电解损毁或微量注射利多卡因对呼吸活动及臂旁内侧核区微量注射吗啡所致呼吸抑制效应的影响。结果是:电解损毀中缝大核区,使呼吸频率增加,膈神经放电的幅度和频率均无明显变化,而臂旁内侧核区微量注射吗啡抑制呼吸的程度减轻;中缝大核区微量注射利多卡因,则部分消除臂旁内侧核区微量注射吗啡的呼吸抑制效应。中缝大核旁网状结构电解损毁或微量注射利多卡因,不影响吗啡的呼吸抑制效应。上述结果提示,中缝大核区可能在脑桥臂旁内侧核区微量注射吗啡抑制呼吸的机制中起一定作用。     

Impairment of Central Chemoreception in Neonatal Rats Induced by Maternal Cigarette Smoke Exposure during Pregnancy

It has been postulated that prenatal cigarette smoke exposure (CSE) increases the risk for sudden infant death syndrome. The victims of infant death syndrome suffer from respiratory abnormalities, such as central apnea, diminished chemoreflex and alteration in respiratory pattern during sleep. However, no experimental evidence on CSE model exists to confirm whether prenatal CSE gives rise to reduction of neonatal central chemoreception in in vitro preparations in absence of peripheral sensory feedback. The aim of the present study was to test the hypothesis that maternal CSE during pregnancy depresses central chemoreception of the neonatal rats. The pregnant rats were divided into two groups, control (n = 8) and CSE (n = 8). Experiments were performed on neonatal (0–3days) rat pups. Fictive respiratory activity was monitored by recording the rhythmic discharge from the hypoglossal rootlets of the medullary slices obtained from the neonatal rats. The burst frequency (BF) and integrated amplitude (IA) of the discharge were analyzed. Their responses to acidified artificial cerebrospinal fluid (aCSF) were tested to indicate the change of the central chemosensitivity. Under condition of perfusing with standard aCSF (pH 7.4), no significant difference was detected between the two groups in either BF or IA (P>0.05). Under condition of perfusing with acidified aCSF (pH 7.0), BF was increased and IA was decreased in both groups (P<0.01). However, their change rates in the CSE group were obviously smaller than that in the control group, 66.98 ± 10.11% vs. 143.75 ± 15.41% for BF and −22.38 ± 2.51% vs. −44.90 ± 3.92% for IA (P<0.01). In conclusion, these observations, in a prenatal CSE model, provide important evidence that maternal smoking during pregnancy exerts adverse effects on central chemoreception of neonates.     

刺激家兔腹部迷走神经外周端降压效应中枢机制的研究

应用电解损毁和脑室内注射药物的方法研究了刺激家兔腹部迷走神经外周端所致降压效应的中枢机制。结果表明:1.电刺激延脑闩部尾侧1.5—2mm、中线旁开0.25mm、深1—2mm 处主要引起降压反应。2.电解损毁该部位可以使刺激腹部迷走神经外周端所引起的降压效应显著减弱(n=20,P<0.001),但对刺激减压神经所致降压反应无影响。3.在延脑闩部水平电解损毁减压神经纤维在孤束核的主要投射区可以使刺激减压神经所致降压反应显著减弱,而对刺激腹部迷走神经外周端所致降压反应无影响。4.第四脑室注射5,6-双羟色胺的动物较之注射人工脑脊液的动物颈、胸髓5-羟色胺含量明显降低、动物动脉压增高、心率明显增快、刺激减压神经所致降压反应未见减弱,而刺激腹部迷走神经外周端所致降压反应却明显减小。因此,我们认为家兔腹部迷走神经外周端所致降压效应依赖于延脑闩下部的中缝隐核及连合核等结构,而与减压神经的投射部位无关。延脑中缝核至脊髓的下行性5-HT能神经纤维抑制脊髓交感节前神经元的活动,是这个降压效应的中枢机制之一。