炎症的自主神经调控与临床意义

Enormous progresses have been made in recent years for the involvement of nervous system in particular the vagus nerve in inflammatory responses. The parasympathetic nerve can be activated by “inflammatory reflex“ to inhibit macrophages, via their specific nicotinic receptor α- 7 subunit, and hence to reduce the production of tumor necrosis factor [TNF) that plays a pivotal role in many inflammatory reactions and is a key mediator for septic shock. This cholinergic anti - inflammatory pathway has been utilized, with positive outcomes, by means of either pharmacological or electrical stimulation in animal models against inflammatory responses and septic shock. Monoclonal antibodies against TNF and other pro- inflammatory cytokines have also been developed and used against inflammation experimentally and clinically. Although clinical use of these new treatments have yielded primitive and only limited results, these new research findings and concepts are important for the advance of modem medicine, as well as for better comprehension of some theories and practices in traditional medicine. Future directions are discussed herewith.     

调节自主神经系统:心血管疾病抗炎治疗的新领域

<正>目前普遍认为高血压、动脉粥样硬化、血脂异常、糖尿病等疾病的发生、发展和转归与炎症免疫反应有着密切联系。同时,心血管疾病中也伴有自主神经病变,表现为交感神经和迷走神经支配紊乱或结构损伤,其主要的病理特征是迷走神经张力减低而交感神经张力亢进。因此,改善自主神经紊乱同时减轻机体低度炎症反应将成为防治心血管疾病的重要方向。近60年的研究表明神经系统可接受免疫系统信号,并可传出神经冲动调节免疫系统活动。     

副流感病毒感染豚鼠咳嗽反射敏感性变化及其神经源性炎症机制探讨

目的: 探讨人副流感病毒Ⅲ型(PIV3)感染豚鼠的咳嗽反射敏感性(CRS)变化和机制,以及神经源性炎症在CRS变化和病毒性咳嗽中的作用。方法: 豚鼠50只,随机分成正常对照组以及病毒感染6、12、28和42 d组;通过滴鼻方法接种PIV3。Buxco肺功能仪测定CRS。免疫荧光和FQ-PCR方法检测PIV3抗原和核酸。ELISA法检测肺组织匀浆的P物质(SP)含量;FQ-PCR检测肺组织SP受体NK1、辣椒素受体亚型1(VR1)的mRNA水平;免疫组化方法检测肺组织SP、VR1和蛋白基因产物(PGP-9.5)的表达及半定量分析,并对它们各自与CRS的相关性进行分析。结果: 各感染组豚鼠CRS均较对照组明显升高,以42 d组为最高。免疫荧光可见PIV3抗原表达;FQ-PCR显示病毒RNA含量在6 d组最高,并随感染时间逐步降低。各组SP和VR1 mRNA,以及12、28和42 d组NK1 mRNA水平均明显高于对照组。6、12及28 d组SP,28和42 d组VR1及42 d组PGP-9.5蛋白表达均增强。相关分析显示,6和28 d组肺匀浆SP含量,12、28和42 d组NK1 mRNA以及各感染组VR1 mRNA均与CRS呈正相关;6、12和42 d组SP的蛋白表达,12和28 d组VR1及12 d组PGP-9.5蛋白表达亦与CRS呈正相关。结论: 神经肽的释放增加提示神经源性炎症的发生。CRS和神经肽的时空变化以及两者的正相关提示神经源性炎症在CRS增高和病毒感染性咳嗽中起重要作用。     

DC固有胆碱能系统与JIA炎症免疫反应的关系

目的 探讨树突状细胞(DC)固有胆碱能系统与幼年特发性关节炎(JIA)炎症免疫反应的关系.方法 分离正常小鼠骨髓细胞,体外采用细胞因子诱导、分化,并刺激其成熟.通过细胞形态变化和表面分子对细胞鉴定;流式细胞术检测正常血清、JLA活动期血清和JIA活动期血清+美加明(MEC)3组血清对DC nAChRα7表达的影响;ELISA方法检测三组血清作用DC 18 h前后,培养上清中IL-12含量;MTT法和流式细胞术分别检测正常血清刺激的DC条件培养液组、JIA活动期血清刺激的DC条件培养液组、MEC干预的JIA活动期血清刺激的DC条件培养液组对小鼠脾淋巴细胞增殖活化的影响.结果 3组血清作用于成熟DC 18 h后DC nAChRα7表达为,JIA活动期血清组比正常血清组明显增强(P<0.05),而MEC作用后,nAChRα7表达有下调趋势;三组血清作用于成熟DC 18 h前后,培养上清中IL-12含量分别为,JIA活动期血清组比正常血清组IL-12含量均明显增高(P<0.01),而培养后,MEC干预组IL-12含量较JIA活动期血清组更高(P<0.05);3组血清刺激的DC条件培养液联合小剂量ConA对小鼠脾淋巴细胞增殖结果(SI值)和CD69表达是,MEC干预组增殖作用和CD69表达最强,JIA活动期血清刺激的DC条件培养液组次之.与正常血清刺激的DC条件培养液组比较增殖作用显著(P<0.01).结论 JIA活动期血清能刺激DC,使nAChRα7表达上调;MEC则下调DC nAChRα7表达,同时,伴有IL-12等炎性因子分泌及淋巴细胞增殖活化增强.故JIA的发生和活化可能与抑制DC胆碱能系统的抗炎作用有关,恢复胆碱能系统的正常调节可能是JIA治疗方向之一.     

基底前脑巢蛋白免疫阳性神经元研究现状及展望

目的阐述基底前脑nestin免疫阳性神经元的研究现状,为后续研究提供依据。方法对近年发表的有关基底前脑nestin免疫阳性神经元的文献进行分析和综述。结果在人和大鼠的基底前脑存在着一群能表达nestin的成熟神经元,这群神经元是区别于胆碱能神经元和γ-氨基丁酸能神经元的独立的神经元。其形态和分布与胆碱能神经元相似,向海马、大脑皮质及丘脑投射,与学习记忆及神经元的可塑性有关。结论基底前脑nestin免疫阳性神经元的化学属性、纤维联系及电生理特征等有待于进一步研究。这些研究将有助于我们了解成熟神经元表达nestin的功能意义,并为相关疾病的诊治提供新的视角。     

胆碱能抗炎通路的机制及其在脓毒症的应用

胆碱能抗炎通路是近年来发现的对全身性炎症反应有调节作用的通路,可通过迷走神经抑制促炎细胞因子的合成从而抑制机体炎症反应.核因子-κB和Janus激酶/信号转导与转录激活子是该通路细胞内信号转导中最重要的两条信号通路.脓毒症以全身炎症反应为特点,是危重症患者的常见死因.根据胆碱能抗炎通路作用迅速有效的特点,推测其可应用于...     

鸡迷走神经传出神经元及其突起的分布

用10只约一年龄的白色来杭鸡,将CB-HRP7μl注入颈部迷走神经干内,动物存活48小时,经主动脉弓处灌流固定。取延髓作40μl厚的冰冻连续切片,TMB法成色。光镜观察。标记的神经元主要位于廷髓的迷走神经背核、疑核及中间带。迷走背核及疑核中的树突都呈放射状分布到周围几个方向。     

胎儿食管肌间神经丛胆碱能神经元的定位定量研究

用引产后死亡的正常胎儿（３２￣４０周，１５个）食管，将其分颈部，胸部上、中、下，腹部食管５部分。对各部位食管肌间神经丛内胆碱能神经元，进行光镜（ｃｈＡＴ、ＡＣｈＥ）和电镜（ＡｃｈＥ）酶组织化学定位、定量观察。结果表明，胆碱能神经元的分布及细胞内酶含量，在食管各部位不同，ＡＣｈＥ在电镜下定位于粗面内质网。这一研究结果，不仅将使食管胆碱能神经支配及其生理功能等基础理论知识，得到进一步阐明、丰富和发展；     

瞬目反射的临床应用研究

本文对26例无脑部病变患者及26例脑部病变的患者分别作了瞬目反射(BlinkReflex BR)的检测。刺激一侧眶上神经,于两侧下眼轮匝肌记录。同侧的两个波为R_1、R_2,对侧的一个波为R′_2。结果脑部病变组双侧R_1、R_2、R_2潜伏期与无脑部病变组比较P值<0.01,有非常显著性差异。提示BR可帮助临床上了解三叉神经、面神经、脑干、丘脑或皮层的机能,可了解病变范围和异常程度,有助于临床定位诊断及药物疗效观察。     

Effects of intestinal inflammation on specific subgroups of guinea-pig celiac ganglion neurons

The consequences of inflammation of a short region of the guinea-pig ileum on the properties of neurons in the celiac ganglia were investigated. Inflammation (ileitis) was induced in 5–8 cm of intestine by the intralumenal injection of trinitrobenzene sulfonate, 6–7 days before tissue was taken. Celiac ganglion neurons were investigated using intracellular microelectrodes and the cells were filled with dye from the recording electrode, to determine their morphologies. Tonic and phasic neurons were identified. In ganglia from normal guinea-pigs and from guinea-pigs with ileitis, cell bodies of tonic neurons were larger and their dendrites were longer and more numerous than those of phasic neurons. Tonic neurons were selectively affected by intestinal inflammation. The number of action potentials elicited by the same intensity of depolarizing current for neurons after ileal inflammation was twice that of neurons from control animals, the threshold current to evoke action potentials was about half, and some of the neurons were spontaneously active. Neurons from untreated or sham-operated animals were never spontaneously active. Many more neurons were affected than project to the 5–8 cm of intestine that was inflamed. We conclude that inflammation of a segment of the ileum causes a selective, humorally mediated, increase in excitability of tonic neurons in the celiac ganglion that control motility and secretion, but not of phasic neurons that project to the intestinal vasculature and other targets.     

A clinico-anatomic study of the auricular branch of the vagus nerve and Arnold’s ear-cough reflex

Summary The results of a clinico-anatomic study of the auricular branch of the vagus nerve (ABVN) and Arnold's ear-cough reflex are presented. The frequency of the ear-cough reflex was found to be 2.3% (12 out of 514 patients). It was bilateral in 3 cases (0.6%). The reflex was elicited by palpation of the postero-inferior wall of the external acoustic meatus (EAM) in 11 patients, and by palpation of the antero-inferior wall in one patient (0.2%). The reflex was frequently noticed to occur after a short latent period. The course of the ABVN inside the jugular foramen (JF), and distribution of the terminal branches of the ABVN in the external acoustic meatus were determined in 8 male cadavers (16 sides). In addition, the length of the mastoid canaliculus (MC) and the relationships of the ABVN with the facial nerve and stylomastoid foramen (SMF) were studied in both cadavers and 25 dry skulls (50 sides). High-resolution computed tomography (HRCT) scanning was also performed in all cadavers prior to microdissections. The ABVN emerged from the superior ganglion of the vagus nerve in all the cadavers. It ran between the internal jugular vein (IJV) and the bony wall of the jugular foramen. The ABVN was encased in a partial bony canal during its course from the jugular foramen to mastoid canaliculus in 18% of all specimens. The average length of the mastoid canaliculus was 5.6 mm (4.2–6.5), and it ran transversely towards the tympanomastoid suture 4.5 mm (4–5.1) above the stylomastoid foramen. The mastoid canaliculus was well demonstrated in all the HRCT scans.

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Etude anatomo-clinique de la branche auriculaire du nerf vague et du réflexe de toux otogène d'Arnold

Résumé Les résultats d'une étude anatomo-clinique concernant la branche auriculaire du nerf vague (BANV) et le réflexe de toux otogène d'Arnold sont exposés. Un réflexe de toux otogène a été trouvé dans 2,3 % des cas (12 cas sur 514). Il était bilatéral dans 3 cas (0,6 %). Le réflexe a été provoqué par la palpation de la paroi postéro-inférieure du méat acoustique externe dans 11 cas. Il a été provoqué après la palpation de sa paroi antéro-inférieure dans 1 cas (0,2 %). Il faut noter que le réflexe est souvent apparu après une brève période de latence. Le trajet de la BANV à l'intérieur du foramen jugulaire et la distribution des branches terminales de la BANV dans le méat acoustique externe ont été précisés sur 8 sujets mâles (16 côtés). De plus, la longueur du canalicule mastoïdien, les rapports de la BANV avec le nerf facial et le foramen stylo-mastoïdien ont été étudiés à la fois sur des sujets anatomiques et sur 25 crânes secs (50 côtés). Une tomodensitométrie à haute résolution a également été réalisée sur tous les sujets anatomiques avant les microdissections. La BANV émergeait du ganglion supérieur du nerf vague sur tous les sujets. Elle passait entre la veine jugulaire interne et le canal osseux du foramen jugulaire. La BANV était enchâssée dans un canal osseux partiel durant son trajet depuis le foramen jugulaire jusqu'au canalicule mastoïdien dans 18 % des cas. La longueur moyenne du canalicule mastoïdien était de 5,6 mm (4,2 – 6,5), et il se dirigeait transversalement vers la suture tympano-mastoïdienne à 4,5 mm (4 – 5,1) au-dessus du foramen stylomastoïdien. Le canalicule mastoïdien a été bien mis en évidence sur toutes les tomodensitométries.

     

下丘脑外侧区对大鼠胃缺血-再灌注损伤调控的神经机制

目的:观察电刺激下丘脑外侧区(LHA)对胃缺血-再灌注损伤(GI-RI)的影响,并初步分析其可能的神经机制。方法:用电和化学刺激、电损毁神经核团及切断外周神经等方法,观察LHA对大鼠胃缺血30min,再灌注60min所致损伤的影响并分析背侧迷走复合体(DVC)、迷走神经和交感神经在这一效应中的作用。结果:①电刺激LHA或LHA内注射L-谷氨酸(L-Glu),GI-RI均显著加重;②电损毁双侧LHA则减轻GI-RI;③损毁双侧DVC能取消电刺激LHA对GI-RI的加重;④分别切断膈下迷走神经和切除腹腔交感神经节后再电刺激LHA,GI-RI则减轻。结论:LHA是对GI-RI具有加重作用的特异性中枢部位,DVC以及迷走神经、交感神经均参与了LHA对GI-RI的调控作用。     

Sympathetic activity in the recto-rectal reflex of the guinea pig

In the guinea pig, defecation is controlled by the myenteric plexus, whose activity is modulated by the sacral spinal and supraspinal centers. The purpose of this study is to clarify the control of defecation reflex by sympathetic nerves. The propulsive contractions of the rectum produced by rectal distension (recto-rectal excitatory reflex response) were abolished after transection of the Th 13 and/or the L 4 segment. This response was reproduced again after removal of the lumbar segments (L1-4), division of the lumbar dorsal roots (L1-4), the lumbar splanchnic nerves or lumbar colonic nerves (LCN). The frequency of efferent discharges of LCN was increased slightly by rectal distension and remarkably increased after Th 13 and/or L 4 transection. Thus, there occurs during the recto-rectal reflex not only mucosal intrinsic reflex and sacral excitatory reflex via the pelvic nerves but also a lumbar inhibitory reflex via the colonic nerves, whose center may be located in the upper lumbar segments.But, the activity of the inhibitory center was depressed by the supraspinal center, so that an excitatory reflex is produced more dominantly than an inhibitory one in normal animals. All these extrinsic reflexes coordinate the activity of the myenteric plexus in defecation reflex.     

40例糖尿病患者神经传导速度和H反射研究

对４０例临床确诊的Ⅱ型糖尿病患者进行了ＮＣＶ测定，其中２０例同时作了Ｈ反射检查。结果显示ＮＣＶ较正常组减慢，异常率为２５％～６５％。下肢异常率高于上肢，ＳＣＶ异常率高于ＭＣＶ，尤以腓浅神经ＳＣＶ最灵敏。研究发现，患者的ＮＣＶ与年龄、血糖值无明显关系，与病程长短呈正相关。Ｈ反射的异常率为８５％，它可反映近髓段神经的功能状态，而ＮＣＶ主要反映远端神经的功能。此两项检查结合临床，使糖尿病性周围神经病的检出率由３８％上升至７６％，并能初步了解神经病变范围。因此ＮＣＶ和Ｈ反射检查对早期诊断糖尿病性神经病变是有价值的。     

Modulation of the Hering-Breuer reflex by raphe pallidus in rabbits

Activation of the pulmonary stretch receptors by lung inflation or vagal stimulation evokes Hering-Breuer (HB) reflex, which is characterized by inspiratory inhibition and expiratory prolongation. In this work, whether the HB reflex could be modulated by the serotonergic raphe pallidus (RP) was studied by comparing the strength of this reflex before and after electrical or chemical stimulation of the RP. Experiments were performed on urethane anesthetized adult rabbits. The HB reflex was simulated with electrical stimulation of the central end of cervical vagus nerve. The RP was stimulated electrically or chemically by microinjection of glutamate. We found that after either electrical stimulation or chemical stimulation of the RP, the inspiratory inhibition and expiratory prolongation of the HB reflex were significantly attenuated. This attenuation showed post-stimulation time dependency or short-term memory, as well as RP stimulation intensity dependency. Results of the present study suggested that the serotonergic RP could exert its respiratory effects by modulating the strength of HB reflex.     

三叉神经-颈反射检测方法的建立及临床意义

目的：建立三叉神经-颈反射的肌电检测方法，探讨其临床应用价值。方法：70例志愿者取卧位，稍抬高头部使胸锁乳突肌轻度收缩，于眶下孔附近刺激，胸锁乳突肌记录。结果：刺激正常受试者一侧的眶下神经，均可记录到双侧胸锁乳突肌反射的正-负波。结论：三叉神经-颈反射测定技术可靠，在下位脑干损伤的定位诊断中有一定帮助。