交感神经节在支配心脏中的作用研究进展

交感神经可支配心脏,并在心脏传导、调节心率、心肌收缩和舒张等方面具有重要作用。目前对支配心脏的交感神经的研究多数集中在心肌组织中分布的交感神经,实际上支配心脏的远端交感神经节(颈部神经节和星状神经节)也发挥着重要作用。文中简要介绍了交感神经节对心脏的支配情况,总结了交感神经节阻滞在心脏疾病治疗中的作用,讨论了交感神经节支配心脏的作用机制方面的研究现况,提出了可以应用细胞电生理、免疫组化分析、分子生物学等技术,对支配心脏的远端交感神经节在心脏疾病、药物及物理因子作用下的机制进行研究。这将对深层次揭示心脏疾病的发病机制及相关治疗药物和物理方法的研制提供一定的理论及实验参考。     

环核苷酸与心血管活动的中枢调节

环核苷酸作为第二信使参与体内许多生理功能的调节。近年来,一些工作证明,交感神经可以通过心肌β受体,促使 cAMP 升高,以提高心肌兴奋性;而迷走神经则可以通过心肌胆硷能受体,增加细胞内cGMP,对抗 cAMP 的作用,从而抑制心肌兴奋性。脑内也广泛分布着环核苷酸及其代谢酶。一些工作证明,环核苷酸在中枢心血管活动的调节中也起着重要作用。给麻醉猫注射 db-cAMP,可以明显提高交感神经兴奋性,使血压升高。最近 Clipsham 等(1980)利用清醒猫进行实验,发现向第三脑室注射 papaverine 和氨茶硷,抑制磷酸二酯酶对环核苷酸的降解作用,可以升高血压,加快心率。而使用磷酸二酯酶激动剂 imidazole-4′-acetic acid     

GATA结合蛋白4在心脏发育及心肌重塑中的作用

转录因子GATA结合蛋白4(GATA-binding protein 4, GATA-4)在心脏发育和心肌重塑过程中发挥重要的调控作用.GATA-4基因缺失可致胚胎死亡,而不同位点的错义突变将引起不同类型的先天性心脏发育畸形.GATA-4蛋白表达水平降低可导致心脏功能进行性下降.压力超负荷、缺氧、交感神经激活等各种心肌肥厚刺激因素均可显著影响GATA-4的DNA结合活性,进而通过调控心房利钠肽(ANP)、脑利钠肽(BNP)、B细胞淋巴瘤因子2(Bcl-2)、心肌锚定重复序列蛋白(CARP)等多种心肌重塑相关转录因子的表达参与心肌重塑过程.深入探讨GATA-4的转录调控机制,有望为心血管疾病的防治提供新的线索.本文扼要综述GATA-4在心脏发育及心肌重塑中的研究现状.     

自主神经系统与机体稳态

<正>自主神经系统是外周神经系统的重要组成部分，包括交感神经系统、副交感神经系统和肠神经系统[1],它在机体的稳态维持中发挥着重要作用。随着交叉组学技术、细胞特异性标记与调控技术、全身神经系统精准成像技术等的综合应用，人们对自主神经系统的精细化结构与功能有了更深入的认识。自主神经系统在从整体观和系统论角度认识机体与环境的相互调控机制方面发挥着重要作用[2]。经典的交感神经系统信息的输出对于维持血压、体温调节和应对外界环境压力至关重要。副交     

特异性microRNAs在心血管系统中的功能研究进展

MicroRNAs(miRNAs)是经核糖核酸酶(Dicer)加工后的一类非编码小RNA分子。在真核生物中,miRNA具有组织特异性和时序性,只在特定的组织和特定的发育阶段表达,在细胞生长和发育过程中起多种作用。miRNAs在心脏发育、形态生成、血管生成、心肌凋亡等多个生理病理过程中发挥重要作用。最近有大量研究发现某些特异性的miRNA对心血管的发育和心血管疾病有一定的影响。如miRNA-126调控血管生成;miRNA-143和miRNA-145决定血管平滑肌(VSMC)的分化和增殖;miRNA-208对心肌肥厚的调节;miRNA-1和miRNA-133影响心肌的发育、形态发生、心肌凋亡、心肌肥厚等。     

氟烷对慢性缺氧兔心肌β肾上腺素能受体的影响

用放射配基结合法和高效液相色谱电化学法分别测定氟烷对慢性缺氧免心肌β肾上腺素能受体（简称β受体）和血浆儿茶酚胺的影响。结果表明：慢性缺氧后兔心肌β受体密度明显下降,受体亲和力无明显变化,血浆肾上腺素、去甲肾上腺素明显升高。缺氧吸入氟烷后兔心肌β受体密度进一步下降,亲和力增加,血浆肾上腺素、去甲肾上腺素无进一步变化。常氧吸入氟烷后心肌β受体密度无明显变化,亲和力升高,血浆肾上腺素、去甲肾上腺素反而降低。结果提示,氟烷抑制常氧兔交感神经活动而不能抑制缺氧兔交感神经活动,氟烷不改变常氧兔心肌β受体密度,但降低缺氧兔心肌β受体密度。β受体密度降低与缺氧后升高的儿茶酚胺下调β受体数目有关,同时可能与氟烷改变了缺氧心肌细胞膜脂质流动性使受体易向膜内移动有关。     

神经递质转运蛋白在应激性心肌病发病中的潜在作用

应激性心肌病是强烈应激诱发的心血管急症,自20世纪90年代初Dote首次报告后,世界各地临床报告病例逐年攀升。发病机制迄今尚不完全清楚,但交感神经过度激活,大量释放去甲肾上腺素在本病发生中起重要作用。根据相关研究进展,主要综述神经递质转运蛋白调控神经递质及交感神经活性在这一神经源性心脏病中可能发挥的重要作用。     

交感神经对青年和老龄小鼠肠道上皮细胞增殖和抗氧化功能的影响

目的 探讨交感神经对青年和老龄小鼠小肠上皮细胞增殖的影响。方法 腹腔注射6-羟多巴胺(6-OHDA)阻断交感神经,用石蜡组织切片和HE染色检测绒毛长度、隐窝深度及两者比值,用免疫组织化学检测增殖细胞核抗原(PCNA)在肠腺中的表达,用试剂盒检测总抗氧化能力(T-AOC)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)等指标。结果 化学性阻断交感神经,在3月龄和18月龄鼠中小肠绒毛长度、V/C比值、小肠肠上皮细胞PCNA表达水平均下降显著,小肠SOD、T-AOC降低,MDA升高。结论 交感神经均能促进3月龄和18月龄鼠小肠上皮细胞的增殖,其中对3月龄小鼠的作用大于18月龄小鼠。     

心肌中t-tubule重构与治疗新策略

心肌横管系统在兴奋收缩偶联中发挥重要作用。随着分子生物学的发展和显微镜分辨率的提高,近年来对横管又有了新的认识。本文主要综述了各类心肌相关疾病的t-tubule重构模式和治疗新策略。     

瞬时受体电位通道与心肌肥大研究进展

瞬时受体电位(transient receptor potential, TRP)通道家族是一类广泛分布于人体各组织和器官的阳离子通道。近年来研究发现,部分表达于心肌细胞的TRP通道亚家族成员在病理性心肌肥大中发挥重要作用,目前关于TRP通道与心肌肥大研究的大量实验结果提示,TRP通道有可能成为干预病理性心肌肥大的重要靶点,TRP通道在病理性心肌肥大中的作用和机制成为一个研究热点。本文主要对参与病理性心肌肥大的TRP通道及其可能机制的最新进展进行综述。     

Learning in the fast lane: new insights into neuroplasticity

The timescale of structural remodeling that accompanies functional neuroplasticity is largely unknown. Although structural remodeling of human brain tissue is known to occur following long-term (weeks) acquisition of a new skill, little is known as to what happens structurally when the brain needs to adopt new sequences of procedural rules or memorize?a cascade of events within minutes or hours. Using diffusion tensor imaging (DTI), an MRI-based framework, we examined subjects before and after a spatial learning and memory task. Microstructural changes (as reflected by DTI measures) of limbic system structures (hippocampus and parahippocampus) were significant after only 2?hr of training. This observation was also found in a supporting rat study. We conclude that cellular rearrangement of neural tissue can be detected by DTI, and that this modality may allow neuroplasticity to be localized over short timescales.     

Diffusion MRI of structural brain plasticity induced by a learning and memory task

Background

Activity-induced structural remodeling of dendritic spines and glial cells was recently proposed as an important factor in neuroplasticity and suggested to accompany the induction of long-term potentiation (LTP). Although T1 and diffusion MRI have been used to study structural changes resulting from long-term training, the cellular basis of the findings obtained and their relationship to neuroplasticity are poorly understood.

Methodology/Principal Finding

Here we used diffusion tensor imaging (DTI) to examine the microstructural manifestations of neuroplasticity in rats that performed a spatial navigation task. We found that DTI can be used to define the selective localization of neuroplasticity induced by different tasks and that this process is age-dependent in cingulate cortex and corpus callosum and age-independent in the dentate gyrus.

Conclusion/Significance

We relate the observed DTI changes to the structural plasticity that occurs in astrocytes and discuss the potential of MRI for probing structural neuroplasticity and hence indirectly localizing LTP.     

Simulating Pancreatic Neuroplasticity: In Vitro Dual-neuron Plasticity Assay

Neuroplasticity is an inherent feature of the enteric nervous system and gastrointestinal (GI) innervation under pathological conditions. However, the pathophysiological role of neuroplasticity in GI disorders remains unknown. Novel experimental models which allow simulation and modulation of GI neuroplasticity may enable enhanced appreciation of the contribution of neuroplasticity in particular GI diseases such as pancreatic cancer (PCa) and chronic pancreatitis (CP). Here, we present a protocol for simulation of pancreatic neuroplasticity under in vitro conditions using newborn rat dorsal root ganglia (DRG) and myenteric plexus (MP) neurons. This dual-neuron approach not only permits monitoring of both organ-intrinsic and -extrinsic neuroplasticity, but also represents a valuable tool to assess neuronal and glial morphology and electrophysiology. Moreover, it allows functional modulation of supplied microenvironmental contents for studying their impact on neuroplasticity. Once established, the present neuroplasticity assay bears the potential of being applicable to the study of neuroplasticity in any GI organ.     

迷路损伤增强大鼠前庭内侧核生长相关蛋白mRNA水平

前庭代偿是研究神经可塑性的一个理想模型。生长相关蛋白（ＧＡＰ－４３）在神经再生和突触重组中起重要作用。用ＤＩＧ标记的ＧＡＰ－４３ ｃＤＮＡ片段作探针进行原位杂交,检测了大鼠迷路损伤５、１２、２０和３０ｄ后前庭内侧核ＧＡＰ－ｍＲＮＡ表达的变化。结果表明,迷路损毁后两侧前庭内侧核ＧＡＰ－４３ｍＲＮＡ的水平以不同的幅度和时程明显升高。这一结果表示,ＧＡＰ－４３ｍＲＮＡ水平的提高可能与前庭代偿中突触重组和     

Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection

Mesenchymal stem/stromal cells (MSCs) are extensively studied as cell-therapy agents for neurological diseases. Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’ neuroprotective functions. Exosomes transfer functional molecules including proteins, lipids, metabolites, DNAs, and coding and non-coding RNAs from MSCs to their target cells. Emerging evidence shows that exosomal microRNAs (miRNAs) play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes. Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis, neurite remodeling and survival, and neuroplasticity. Thus, exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke, traumatic brain injury, and neuroinflammatory or neurodegenerative diseases and disorders. This review discusses the neuroprotective effects of selected miRNAs (miR-21, miR-17-92, miR-133, miR-138, miR-124, miR-30, miR146a, and miR-29b) and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders. It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes, optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.     

血管重构及其药物治疗

血管重构是血管为适应内外环境变化而发生的结构和功能改变。这个过程包括血管壁细胞的增生、肥大、凋亡、细胞迁移、细胞外基质的产生及降解等细胞生物学变化。血管重构可分为肥厚性血管重构与非肥厚性血管重构,两者以一定比例共存于同一血管上。非肥厚性血管重构的主要特征是血管外径明显减少、内径明显减少,中膜横截面积不变,血管平滑肌细胞发生重排;肥厚性血管重构的主要特征是内径明显减少,中膜横截面积增加,血管平滑肌细胞增生。血管重构既是高血压和动脉粥样硬化等相关疾病恶化的重要病理基础或也是此类疾病发生发展的病因。药物治疗不仅要缓解或消除相关疾病的症状,更重要的是逆转或减轻血管重构,保护靶器官。     

Cell line differences in replication timing of human glutamate receptor genes and other large genes associated with neural disease

There is considerable current interest in the function of epigenetic mechanisms in neuroplasticity with regard to learning and memory formation and to a range of neural diseases. Previously, we described replication timing on human chromosome 21q in the THP-1 human cell line (2n = 46, XY) and showed that several genes associated with neural diseases, such as the neuronal glutamate receptor subunit GluR-5 (GRIK1) and amyloid precursor protein (APP), were located in regions where replication timing transitioned from early to late S phase. Here, we compared replication timing of all known human glutamate receptor genes (26 genes in total) and APP in 6 different human cell lines including human neuron-related cell lines. Replication timings were obtained by integrating our previously reported data with new data generated here and information from the online database ReplicationDomain. We found that many of the glutamate receptor genes were clearly located in replication timing transition zones in neural precursor cells, but this relationship was less clear in embryonic stem cells before neural differentiation; in the latter, the genes were often located in later replication timing zones that displayed DNA hypermethylation. Analysis of selected large glutamate receptor genes (>200 kb), and of APP, showed that their precise replication timing patterns differed among the cell lines. We propose that the transition zones of DNA replication timing are altered by epigenetic mechanisms, and that these changes may affect the neuroplasticity that is important to memory and learning, and may also have a role in the development of neural diseases.     

SHH信号通路在海马神经可塑性及相关神经系统疾病中的作用

音猬因子（sonic hedgehog,SHH）是一种分泌蛋白质,可在发育过程中控制神经祖细胞、神经元和神经胶质细胞的形成。研究发现,海马是学习和记忆中至关重要的大脑区域,SHH在海马神经元回路的形成和可塑性中发挥重要作用,可介导海马神经的发生和突触的可塑性调节。海马神经元树突中SHH受体的激活是跨神经元信号通路的组成部分,该信号通路可加速轴突的生长并增强谷氨酸从突触前末端的释放。SHH信号通路转导受损可导致中枢神经系统损伤和相关疾病（如自闭症、抑郁症和神经退行性疾病等）发生。因此,控制SHH信号通路转导,如使用SHH通路抑制剂或激动剂可能有助于相关疾病的治疗。综述了SHH信号通路的海马神经可塑性及其在中枢神经系统发育和相关疾病中的影响,以期为阐明SHH信号转导受损导致的海马神经受损和中枢神经系统相关疾病的机制奠定一定的理论依据。     

ORAI channels in cellular remodeling of cardiorespiratory disease

Cardiorespiratory disease, which includes systemic arterial hypertension, restenosis, atherosclerosis, pulmonary arterial hypertension, asthma, and chronic obstructive pulmonary disease (COPD) are highly prevalent and devastating diseases with limited therapeutic modalities. A common pathophysiological theme to these diseases is cellular remodeling, which is contributed by changes in expression and activation of ion channels critical for either excitability or growth. Calcium (Ca²⁺) signaling and specifically ORAI Ca²⁺ channels have emerged as significant regulators of smooth muscle, endothelial, epithelial, platelet, and immune cell remodeling. This review details the dysregulation of ORAI in cardiorespiratory diseases, and how this dysregulation of ORAI contributes to cellular remodeling.