Inhibition of Glial Activation in Rostral Ventromedial Medulla Attenuates Mechanical Allodynia in a Rat Model of Cancer-induced Bone Pain

Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical compo-nent of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotro-phic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and ?uorocitrate) into CIBP rats' RVM could reverse the glial activation and significantly attenuate me-chanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of pro-inflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.

Postsynaptic responses of the thoracic sympathetic preganglionic neurons to electrical stimulation of the rostral ventrolateral medulla in cats

Objective: To study the characteristics of the postsynaptic potentials in thoracic sympatheticpreganglionic neurons (SPNs) evoked by electrical stimulation of the rostral ventrolateral medulla (RVLM ) incats. Methods: In 11 α--chloralose/urethane anesthetized, artificially ventilated cats, intracellular recordings weremade from T, spinal cord with microelectrodes filled with 3 mol/L KCl. SPNs were identified by antidromicstimulation of the T3 white ramus. Results: Twenty--four SPNs were recorded, the resting membrane potentials ofwhich ranged between -- 45 -- -- 90 mV. The onset latency and threshold of the antidromic action potentialsaveraged (6. 48 + 0. 89) ms and (2. 86 + 0. 37) V respectively. Single pulse (0. 2 ms. 50-- 300 PA) electricalstimulation of RVLM evoked fast excitatory postsynaptic potentials (eEPSPs) with short latencies (4--47 ms) inall the 24 SPNs. In 11 of the SPNs, EPSPs with longer latencies (IEPSPs, 70-- 140 ms) were also recorded. Mostof the eEPSPs and some of the IEPSPs were typical monosynaptic EPSPs as they were of constant onset latency.Conclusion: The results provided direct physiological evidence for that some RVLM sympathoexcitatory neuronsproject monosynaptically to thoracic SPNs. The descending pathways from RVLM may consist of two distinctgroups of fibers, the conduction velocities were calculated to be 5--25 m/s and 0. 78-- 1. 6 m/s respectively.

A comparative analysis of differentially expressed genes in rostral and caudal regions after spinal cord injury in rats

The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development.The differences between the rostral and caudal regions around an SCI lesion have received little attention.Here,we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI.We identified a set of differentially expressed genes,including Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1,between rostral and caudal regions at different time points following SCI.Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus,blood vessel development,and brain development.We then chose Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation.Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas,providing new insights into the pathology of SCI.

Sweet and Bitter Tastes Evoked Different Neuronal Activation in the Rostral Portion of the Nucleus of the Solitary Tract of Developing Rats

The impact of the gustatory stimuli on the rostral portion of the nucleus of the solitary tract (rNST) was investigated in developing rats, by using c-fos immunohistochemical staining. Wistar male rats of 5, 15, and 25 days of age were isolated from the mother for 12 h, then stimulated via the intraoral route with quinine, sucrose, or NaCl, and sacrificed 90 min later. The water-stimulated group showed minimal c-fos-like immunoreactivity (FLI) compared with taste-stimulated groups that exhibited different FLI in the rNST at the different ages. At all ages the quinine-stimulated group induced FLI in the medial subfield, while sucrose induced FLI in the lateral subfield of the rNST. The intensity of FLI was highest at P15, and it declined at P25. These findings provide detailed insight into the anatomical basis of rNST activation that is involved in early food intake and the learning capacity of the newborn.

Melanocortin-4 Receptor Expression in the Rostral Ventromedial Medulla Involved in Modulation of Nociception in Transgenic Mice

The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.

A tissue-engineered rostral migratory stream for directed neuronal replacement

New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mammalian brain—including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-engineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient's own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replacement following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-principle evidence that it promotes and directs migration of immature neurons.

Global Transcriptional Profile of Tranosema rostrale Ichnovirus Genes in Infected Lepidopteran Hosts and Wasp Ovaries

The ichnovirus TrIV, transmitted by the endoparasitic wasp Tranosema rostrale to its lepidopteran host during oviposition, replicates asymptomatically in wasp ovaries and causes physiological dysfunctions in parasitized caterpillars. The need to identify ichnoviral genes responsible for disturbances induced in lepidopteran hosts has provided the impetus for the sequencing and annotation of ichnovirus genomes, including that of TrIV. In the latter, 86 putative genes were identified, including 35 that could be assigned to recognized ichnoviral gene families. With the aim of assessing the relative importance of each TrIV gene, as inferred from its level of expression, and evaluating the accuracy of the gene predictions made during genome annotation, the present study builds on an earlier qPCR quantification of transcript abundance of TrIV rep ORFs, in both lepidopteran and wasp hosts, extending it to other gene families as well as to a sample of unassigned ORFs. We show that the majority (91%) of putative ORFs assigned to known gene families are expressed in infected larvae, while this proportion is lower (67%) for a sample taken among the remaining ORFs. Selected members of the TrV and rep gene families are shown to be transcribed in infected larvae at much higher levels than genes from any other TrIV gene family, pointing to their likely involvement in host subjugation. In wasp ovaries, the transcriptional profile is dominated by a rep gene and a member of a newly described gene family encoding secreted proteins displaying a novel cysteine motif, which we identified among previously unassigned ORFs.

Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation

The rostral agranular insular cortex(RAIC)has been associated with pain modulation.Although the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive under the neuropathic pain state.Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve(CPN)ligation.The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice,glutamatergic,or GABAergic neuron cannabinoid receptor 1(CB1R)knockdown mice with the whole-cell patch-clamp and pain behavioral methods.The E/I ratio(amplitude ratio between mEPSCs and mIPSCs)was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice.Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice.The analgesic effect of ACEA(a CB1R agonist)was alleviated along with bilateral dorsolateral funiculus lesions,with the administration of AM251(a CB1R antagonist),and in CB1R knockdown mice in GABAergic neurons,but not glutamatergic neurons of the RAIC.Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.

RVM致炎细胞因子上调导致5-HT释放参与调控慢性术后疼痛

【目的】探讨延髓头端腹内侧部(RVM)内致炎细胞因子肿瘤坏死因子α(TNFα)和白介素-1β(IL-1β)释放增多导致5-羟色胺(5-HT)向脊髓释放增多在慢性术后疼痛(CPSP)模型中的作用。【方法】按照随机方式将SD大鼠进行如下分组:对照组、皮肤/肌肉切开和牵拉(SMIR)(1d,7d)组、SMIR+RVM内注射TNFα或IL-1β中和性抗体组、SMIR+RVM内注射TNFα或IL-1β组、SMIR+RVM内注射溶剂组,用up-down方法测量大鼠50%机械刺激撤足阈值,免疫组化检测RVM内TNFα或IL-1β表达情况,酶联免疫吸附测定法(ELISA)方法观察RVM及脊髓背角内5-HT含量的变化。【结果】SMIR可引起大鼠机械痛敏,表现为50%机械刺激撤足阈值下降,持续至少3周。SMIR后,RVM内神经元和星形胶质细胞中的TNFα和IL-1β表达上调。TNFα或IL-1β中和抗体(每天一次行SMIR术前30 min给予,共4次))微量注射入RVM可阻断SMIR引起的50%机械刺激撤足阈值下降,并可降低RVM及脊髓背角5-HT的含量。正常动物RVM内注射TNFα和IL-1β也可导致50%机械刺激撤足阈值下降,且引起RVM及脊髓内5-HT含量增加。【结论】RVM中致炎细胞因子增多可能通过引起5-HT释放增多参与调控SMIR后慢性术后疼痛的发生发展。

Activation of glycine site and GluN2B subunit of NMDA receptors is necessary for ERK/CREB signaling cascade in rostral anterior cingulate cortex in rats:Implications for affective pain

Objective The rostral anterior cingulate cortex(rACC)is implicated in processing the emotional component of pain.N-methyl-D-aspartate receptors(NMDARs)are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)and/or extracellular regulated kinase(ERK)/cAMP-response element-binding protein(CREB).The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC.Methods Immunohistochemistry and Western blot analysis were used to separately assess the expression of phospho-ERK(pERK)and phospho-CREB(pCREB)in vitro and in vivo.Double immunostaining was also used to determine the colocalization of pERK and pCREB.Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC,which was inhibited by the NMDAR antagonist DL-2-amino-5-phospho-novaleric acid.Selective blockade of the NMDAR GluN2B subunit and the glycinebinding site,or degradation of endogenous D-serine,a co-agonist for the glycine site,significantly decreased the up-regulation of pERK and pCREB expression in the rACC.Further,the activated ERK predominantly colocalized with CREB.Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats,and these might be fundamental molecular mechanisms underlying pain affect.

Correlation between cerebral cortex changes and clinical features in patients with neuromyelitis optica spectrum disorder with normal-appearing brain tissue:a case-control study

Neuro myelitis optica spectrum disorder(NMOSD) is an inflammatory demyelinating disease of the central nervous system.However,whether and how cortical changes occur in NMOSD with normal-appearing brain tissue,or whether any cortical changes correlate with clinical chara cteristics,is not completely clear.The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age,sex,and educational background from December 2020 to February 2022.A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness,sulcal depth,and gyrification index.Analysis showed that cortical thickness in the bilate ral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants.Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes,those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus,superior parietal co rtex,and pericalcarine co rtex.Correlation analysis indicated that co rtical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale.These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue,and that the degree of thinning is correlated with clinical disability and cognitive function.These findings will help im prove our understanding of the imaging chara cteristics in NMOSD and their potential clinical significance.

N-甲基-D-天冬氨酸受体/MAPK/环磷腺苷效应元件结合蛋白通路在前扣带皮层介导痛相关情绪

目的探讨N-甲基-D-天冬氨酸(NMDA)受体/MAPK/环磷腺苷效应元件结合蛋白(CREB)通路参与前扣带皮层介导痛相关情绪的机制。方法选取健康SD大鼠共42只,随机分为空白对照组(Ctrl)、脚掌注射生理盐水(NS)组、脚掌注射完全弗氏佐剂(CFA)模型组(CFA)、脚掌注射CFA及前扣带皮层吻侧部(rACC)中注射NS组(CFA+NS)、脚掌注射NS及rACC中注射NS组(NS+NS)、脚掌注射CFA及rACC内注射NMDA受体拮抗剂(APⅤ)组(CFA+APⅤ)、脚掌注射NS及rACC内注射APⅤ组(NS+APⅤ),每组n=6只。分析大鼠回避分数及观察大鼠热缩足潜伏期(PWL),采用免疫组织化学染色检测脑rACC区NMDA受体表达;免疫荧光染色检测脑rACC区NMDA受体、磷酸化ERK(p-ERK)、磷酸化CREB(p-CREB)表达;尼氏染色观察脑rACC区尼氏小体数量;Western blotting检测rACC区NMDA受体、MAPK、CREB、ERK、p-ERK、p-CREB、突触小体相关蛋白25的相互作用蛋白30(SIP30)蛋白表达;Real-time PCR检测脑rACC区NMDA受体、MAPK、CREB、ERK的mRNA表达。结果与Ctrl组比较,CFA组大鼠回避分数及PWL明显降低,NMDA受体、MAPK、CREB表达明显增加(P<0.05);与CFA+NS组比较,CFA+APⅤ、NS+APⅤ组尼氏小体数量明显升高,NS+NS、NS+APⅤ组NMDA受体、MAPK、CREB、p-ERK、p-CREB表达明显降低(P<0.05)。结论rACC中的NMDA受体/MAPK/CREB信号通路参与了痛相关情绪,抑制NMDA可减轻痛相关负情绪。

头足类年龄与生长特性的研究方法进展

头足类是软体动物门的重要类群,了解头足类的年龄和生长特性,有助于掌握其生活史、估算种群数量及其资源变动。研究头足类年龄和生长的方法主要有长度频度分析法,利用角质颚的长度及其轮纹、耳石的结构及轮纹、内壳等。长度频度分析法并不太适合用来研究生命周期短、生长快的头足类,耳石等硬质材料因其具有生长轮纹且信息较为稳定而被广泛应用。头足类的年龄与生长研究是一个极为复杂的生物学问题,同一种类不同种群个体之间生长差异明显,因此,在以后的研究过程中,可以根据年龄、捕获日期等资料先分种群,然后按各种群分别研究其生长特性。

Pax-6在大鼠发育脑喙侧神经干细胞迁移流中的表达

目的 了解大鼠脑发育过程中 ,喙侧神经干细胞迁移流中不同时期Pax 6表达水平的时空差异。 方法 用BrdU对胚胎 14d、出生后 0、1和 7d的Wistar大鼠行活体标记 ,取各时相点鼠脑 ,冰冻切片 ,行BrdU、Nestin、Pax 6和胶质纤维酸性蛋白 (GFAP)免疫荧光染色 ,观察Pax 6在脑内增殖细胞中的表达情况 ,比较在上述 4个时相点 ,Pax 6于室管膜前下区、迁移流主干部分和嗅球 3个部分的表达差异。 结果 1 在发育中大鼠脑内 ,Pax 6主要表达于神经干细胞内 ,在海马增殖细胞亦有较高表达。 2 在喙侧神经干细胞迁移流内 ,Pax 6在迁移流主干部分的表达高于室管膜前下区和嗅球 ;在胚胎 14d的表达与出生后 0d和 1d相似 ,表达水平较高 ,出生后 7d迅速下降到很低水平。 结论 在大鼠脑发育过程中 ,Pax 6主要表达于神经干细胞及海马增殖性细胞内 ,在大鼠出生后 ,随着大鼠脑的发育 ,Pax 6于喙侧神经干细胞迁移流的表达迅速减弱 ,但迁移流主干部分的表达始终高于室管膜前下区和嗅球。

大鼠心率变异性频谱中高频成分的中枢机理分析

本文探讨心率变异性（heartratevariability，HRV）频谱中高频成分的中枢机理。对正常SD大鼠给予不同频率的人工通气并电刺激延髓疑核，观察HRV频谱的改变，记录与呼吸节律同步的延髓头端腹外侧区（rostralventrolateralmedulla,rVLM）及其周围区神经元细胞外单位放电，对HRV和放电变异性进行相干函数分析。结果显示：（1）HRV的高频成分的中心频率随着人工通气频率的增加而增加，呈高度线性相关，（r=0.83，P＜0．0001）；（2）对rVLM及其周围区与呼吸节律同步的神经元细胞外单位放电和HRV同时进行频谱分析，两者的高频峰呈良好的相关，相干系数k2=0．854±0．1；（3）间断电刺激延髓疑核时，HRV高频成分显著增加。实验直接提示rVLM区参与对HRV的高频调节，HRV的高频成分反映了迷走中枢的波动性活动。

中枢一氧化氮对心血管作用的多样性研究

目的观察一氧化氮(nitric oxide,NO)在心血管中枢孤束核(NTS)和头端延髓腹外侧区(RVLM)内的心血管作用特点,从而明确其在介导中枢心血管功能调控中的意义。方法采用微量注射的方法观察麻醉SD大鼠NTS和RVLM增加或降低NO后动物血压、心率和肾交感神经活动的变化。结果在麻醉SD大鼠模型上,在心血管反射传入的中继站NTS内微量注射NO前体L-精氨酸(L-Arg,2nmol/50nl)能降低基础血压、心率和肾交感神经活动(P<0.05),而注射NO合酶(NOS)抑制剂NG-硝基-L-精氨酸甲酯(L-NAME,10nmol/50nl)能增加心血管功能(P<0.05)。在交感输出的关键区域RVLM注射L-Arg(2nmol/100nl)能增加血压、心率和交感神经活动(P<0.05),而给予L-NAME(10nmol/100nl)则抑制心血管功能(P<0.05)。结论 NO在不同的心血管中枢中具有不同的作用,提示其多样性效应对维持基础心血管功能具有特定的意义。

内阿片肽在“双固一通”针法保护缺血心肌中的作用

目的探讨延髓头端腹外侧区(rVLM)内阿片肽在"双固一通"针法电针对家兔心肌缺血损伤保护效应中的作用。方法本研究在"双固一通"针法对家兔急性心肌缺血保护作用的基础上,观察rVLM内微量注射纳洛酮后电针对急性心肌缺血家兔心电图及心肌细胞超微结构的影响。结果 rVLM内微量注射纳洛酮对正常家兔心肌功能和结构无明显影响,"双固一通"针法电针对缺血心肌具有一定的保护作用,能显著改善心肌缺血时心肌超微结构和心电图的变化(P<0.05),该作用可被纳洛酮所减弱(P<0.05),但不具有完全阻断作用。结论 "双固一通"针法对急性缺血心肌细胞具有保护效应,其作用与rVLM内源性阿片肽系统的介导有关。

针刺或褪黑素的中枢降压作用与延髓氨基酸递质改变的关系

目的研究针刺降压和褪黑素(Mel)在下丘脑前核(AHA)引起应激性高血压大鼠血压降低的作用是否与延髓头端腹外侧区(rVLM)氨基酸类递质释放的改变有关,并分析Mel降压机制与针刺降压机制之间的关系。方法采用足底电击结合噪声的方法建立应激性高血压大鼠模型;针刺应用电针的方法,穴位取双侧足三里;采用中枢核团微量注射的方法给药,观察动脉血压的改变,同时应用脑内微透析的方法取样,并利用高效液相色谱-荧光检测的方法,分析透析液中氨基酸含量的改变。结果大鼠在接受应激处理后,血压升高,同时,rVLM内谷氨酸(Glu)释放量增加,应激性高血压大鼠在经针刺处理后,血压回降,同时,rVLM内Glu释放量回减。微量注射Mel至应激性高血压大鼠的AHA能使血压降低,同时,rVLM内Glu释放量也减少,而γ-氨基丁酸(GABA)和牛磺酸(Tau)释放量则增加。在rVLM微量注射GABAA受体拮抗剂荷包牡丹碱(bicuc)则可部分阻断Mel在AHA引起的降压效应。结论针刺降压与rVLM内Glu释放量减少有关,而Mel在AHA引起的降压效应则与rVLM内Glu释放量减少,以及GABA和Tau释放量增加有关。针刺降压和Mel在AHA引起的降压机制都与rVLM内Glu释放量减少有关。

罗非鱼脑垂体结构研究——Ⅰ.腺垂体前叶的超微结构

本文研究尼罗非鲫Oreochromis nilotica腺垂体前叶的超微结构。前叶主要由促肾上腺皮质激素分泌细胞(ACTH)、催乳激素分泌细胞(PRL)和一种非分泌类型的星状细胞(SC)所构成。对脑垂体结构的周年观察,表明在产卵期间ACTH细胞和PRL细胞均高度活跃,ACTH的分泌可能促进排卵活动,而PRL的分泌活动则受温度变化的影响。腺垂体前叶只接受B型神经分泌纤维的直接支配,星状细胞和Ⅱ型脑垂体细胞则参与腺细胞分泌颗粒的释放和运输等活动。本文并讨论了腺细胞的分泌颗粒通过胞吐和扩散两种方式释放等特点。

salusin α在孤束核内的心血管效应可能通过抑制头端延髓腹外侧区前交感神经元活动介导

目的探讨孤束核内salusinα的心血管效应及其机制。方法♂SD大鼠94只,其中50只大鼠单侧NTS或双侧NTS注射不同剂量salusinα(0.04～4 pmol)或人工脑脊液(artificial cerebrospinal fluid,aCSF),观察NTS内salusinα对大鼠血压和心率产生的影响。33只大鼠分别预先在NTS给予aCSF、非选择性谷氨酸受体拮抗剂犬尿希酸(KYN)、双侧颈部迷走神经切断(bilateral vagotomy)或在头端延髓腹外侧区(RVLM)给予aCSF/GABA受体激动剂muscimol,探讨NTS内salusinα的心血管效应机制。11只大鼠检测NTS水平salusinα对大鼠动脉压力反射(arterial baroreflex,ABR)功能的影响。结果在NTS双侧或单侧微量注射salusinα产生剂量依赖性的降低血压、减缓心率的作用。双侧微量注射salusinα不影响麻醉大鼠的ABR。NTS预先注射KYN(1nmol)或双侧迷走神经切除均不影响孤束核注salusinα产生的降低血压、减缓心率的效应(P>0.05)。RVLM预先注射muscimol(5 pmol)能有效阻断salusinα(4 pmol)在孤束核产生的降低血压、减缓心率的效应(P<0.05)。结论 NTS注射salusinα产生的降低血压、减缓心率的效应可能通过激动RVLM内GABA受体,抑制前交感神经元兴奋性发挥作用。