红景天预防阿尔茨海默病的效果和机理研究进展

阿尔茨海默病（AD）是一类进行性的、不可逆的精神退行性病变,能干扰意识、智能的活动。这些神经系统退行性病变的具体发生机制目前尚不清楚,但患者大脑内的神经细胞功能丢失、淀粉样结构的反常积累、含磷酸基蛋白（tua蛋白）的过磷酸化、线粒体组成和功能不良、慢性炎症反应、氧化应激等,目前都被认为是这些病症中最常见的病理学特点,而认知与学习记忆能力下降、执行功能障碍也是重要的临床表现。多项科学研究表明,传统中药红景天中的许多化学物质如红景天苷、红景天素等,都能够通过抗氧化、抗炎症、抗细胞凋亡等药理学手段,对AD类神经系统退行性病变产生优异的神经防护作用。     

红景天苷防治帕金森病的药理作用研究进展

帕金森病已成为威胁老年人身心健康的主要疾病之一。红景天苷是从红景天中提取的主要活性化合物之一，具有多种药理作用。红景天苷可通过抑制细胞凋亡、增强细胞自噬、降低氧化应激反应、降低炎症反应、促进胶质细胞源性神经营养因子的表达、提高多巴胺转运蛋白的表达以达到防治帕金森病的作用。总结了红景天苷防治帕金森病的药理作用及其作用机制，为红景天苷的临床使用提供参考。     

红景天苷对肾脏保护作用的药理机制研究进展

药理学研究已经证实红景天苷具有抗炎、抗肿瘤、免疫调节、促进骨和骨骼肌生长、抗氧化、增体质以及抗疲劳、抗肌萎缩、抗骨质疏松、抗痴呆和保护肝脏、神经、肺、呼吸道、心脏、血管的作用,以及具有降血糖、调血脂、抗肥胖等药理作用。综述红景天苷保护肾脏作用的研究资料,并认为红景天苷极有可能被开发成防治代谢综合征、心脑血管病及其并发症药物,并对其药理机制研究进展做了分析。     

红景天苷药理作用研究进展概述

摘 要红景天苷是中药红景天中提取的一种苯乙醇类化合物,为红景天主要有效成分。具有多种药理作用,应用前景广泛。本文主要从红景天苷对心血管系统、神经、肝脏、皮肤的保护作用等几个方向对其药理作用进行综述,为相关疾病的药物防治研究与临床应用提供理论依据。     

红景天苷对神经干细胞作用的研究

目的:观察红景天苷药物血清对新生大鼠海马神经干细胞分化为神经元的影响。方法:从新生24h内的W istar大鼠脑中分离扩增获得大量神经干细胞后,加入低、中、高剂量的红景天苷药物血清,观察其对神经干细胞分化为神经元的影响,并通过免疫细胞化学染色检测神经干细胞分化为神经元的状况。结果:低、中、高剂量的红景天苷药物血清组单位视野内神经元特异烯醇化酶(N SE)阳性细胞个数与对照组相比有显著差异(P<0.01),并呈一定的剂量依赖性。结论:红景天苷药物血清在体外可促进神经干细胞向神经元方向分化,为红景天药物应用于相关神经系统疾病的临床治疗提供了试验依据。     

红景天苷在疾病中的作用及机制研究进展

摘要：红景天苷是苯丙素类糖苷,作为高原植物红景天的主要有效成分。近3年来,红景天苷许多疾病(代谢综合征、心脑血管疾病、神经系统疾病及肿瘤)中的作用及作用机制备受关注。研究显示红景天苷有预防及治疗此类疾病发生的潜力。本文综述了红景天苷在疾病中的作用及机制,以期为红景天苷的研究与开发提供新的思路和依据。     

红景天苷心肌保护作用机制的研究进展

红景天苷是景天科植物大花红景天的主要活性成分,存在于该植物的根及根茎中。大量的研究证明,红景天苷具有多种药理学作用,包括显著的抗氧化、抗炎、抗纤维化,改善心功能等作用。近年来,有许多关于红景天苷的药理研究,但红景天苷在心血管疾病中的应用及其机制研究仍然欠缺。本综述介绍红景天苷心肌保护作用机制的研究进展。     

红景天苷药理作用及机制

红景天系蔷薇目景天科红景天属多年生草本或亚灌木野生植物,红景天苷是红景天最有效的活性成分之一,不仅有抗疲劳、抗衰老、免疫调节、清除自由基、增强记忆改、善睡眠等药理作用,还可以起到保护心脏,抵抗辐射对人体的伤害,保护保护造血系统的药理作用。本文综述了近年来国内外对红景天苷对心、脑、肾、肝、神经、皮肤的作用其和药理方面的研究,以其为红景天苷的进一步开发、利用提供参考。     

西红花苷防治中枢神经系统疾病的研究进展

西红花苷是西红花中活性成分，具有多种药理作用。西红花苷具有出色的中枢神经系统保护作用，可以多维度、多途径地改善中枢神经系统疾病的神经功能，能抗抑郁、抗癫痫，对帕金森病、阿尔茨海默病、缺血性脑卒中、多发性硬化具有神经保护作用。综述了西红花苷防治中枢神经系统疾病的研究进展，以期提高西红花苷在临床治疗中的转化和应用。     

红景天苷减轻叠氮钠诱导线粒体损伤的作用

目的观察红景天苷对呼吸链复合体IV抑制剂叠氮钠(NaN₃)诱导的线粒体损伤的保护作用，探讨其在防治神经退行性疾病中可能的作用机制。方法将叠氮钠与人神经母细胞瘤细胞株SH-SY5Y共同孵育，MTT法测定细胞存活力，JC-1法检测线粒体膜电位变化。刃天青法检测大鼠脑线粒体功能。结果64 mmol·L^-1叠氮钠与SH-SY5Y共同孵育4 h后，细胞存活率明显下降，线粒体膜电位下降。预先加入红景天苷能明显提高细胞存活率，维持线粒体膜电位。650 μmol·L^-1叠氮钠能使大鼠脑线粒体功能下降，预先加入红景天苷能明显改善线粒体功能。结论红景天苷能够减轻叠氮钠(NaN₃)诱导的线粒体损伤，能够改善线粒体功能，这可能是其抗老年痴呆的机制之一。     

Alzheimer's disease amyloid hypothesis at crossroads: where do we go from here?

Alzheimer's disease has been the focus of several drug discovery approaches by the pharmaceutical industry. Four drug candidates coming out of such efforts have recently failed in late-stage clinical trials for lack of efficacy or safety concerns. These drugs were designed based on the presently dominant scientific hypothesis for Alzheimer's disease called the ‘amyloid hypothesis’. This editorial will briefly review the failure of these drugs and the effect of this on the amyloid hypothesis. Rather than accept the status quo, this editorial suggests a revised version of this hypothesis to reconcile data from recent drug failures. We propose a two-phase disease process; a first phase that is independent of amyloid and a second robust phase dependent on the amyloid cascade. Further validation of this revised hypothesis could aid future drug discovery for this devastating disease.     

Neuronal 5-HT receptors in the periphery

5-Hydroxytryptamine (5-HT) induces responses in neurones from all branches of the mammalian peripheral nervous system. Responses may be excitatory or inhibitory and are mediated through at least four distinct receptor sites.One receptor mediates excitation in motoneurones and preganglionic sympathetic neurones and can be designated a D (or possibly 5-HT₂) receptor since “classical” antagonists such as methysergide, metergoline or cinanserin are potent and selective antagonists at this site. A second receptor mediating neuronal excitation can be positively identified on the basis of susceptibility to blockade by small concentrations of 1αH,3α,5αH-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222) and the weak or negligible affinity, relative to 5-HT, of certain agonists such as 5-methoxytryptamine. Such sites mediate depolarization of sympathetic and parasympathetic neurones and excitation of both the cell bodies and terminals of primary afferent fibres. A third receptor, mediating neuronal excitation, is the classical M-receptor of Gaddum and Picarelli, at this stage clearly identified only on postganglionic parasympathetic neurones of the guinea-pig myenteric plexus. These sites can be differentiated from other excitatory 5-HT receptors since MDL 72222 is neither potent nor selective as an antagonist and 5-methoxytryptamine approaches the potency of 5-HT as an agonist. (3α-Homotropanyl)-1-methyl-5-fluoro-indole-3-carboxylic acid is a potent, surmountable antagonist of 5-HT at the M-receptor of the ileum, but is non-selective.Neuronal inhibitory responses have been observed using electrophysiological techniques or by monitoring the decrease in depolarization-evoked release of transmitter in enteric, parasympathetic and sympathetic neurones. Largely negative results, using selective agonists and antagonists, allow the receptor(s) mediating inhibition to be clearly differentiated from the three neuronal excitatory receptors for 5-HT. Comparison of relative potencies of agonists suggests similarities with the 5-HT₁ recognition site of the central nervous system; no selective antagonist has yet emerged to permit their positive identification.     

The anti-cancer agent SU4312 unexpectedly protects against MPP+-induced neurotoxicity via selective and direct inhibition of neuronal NOS

Background and Purpose

SU4312, a potent and selective inhibitor of VEGF receptor-2 (VEGFR-2), has been designed to treat cancer. Recent studies have suggested that SU4312 can also be useful in treating neurodegenerative disorders. In this study, we assessed neuroprotection by SU4312 against 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity and further explored the underlying mechanisms.

Experimental Approach

MPP⁺-treated neurons and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated zebrafish were used to study neuroprotection by SU4312. NOS activity was assayed in vitro to examine direct interactions between SU4312 and NOS isoforms.

Key Results

SU4312 unexpectedly prevented MPP⁺-induced neuronal apoptosis in vitro and decreased MPTP-induced loss of dopaminergic neurons, reduced expression of mRNA for tyrosine hydroxylase and impaired swimming behaviour in zebrafish. In contrast, PTK787/ZK222584, a well-studied VEGFR-2 inhibitor, failed to prevent neurotoxicity, suggesting that the neuroprotective actions of SU4312 were independent of its anti-angiogenic action. Furthermore, SU4312 exhibited non-competitive inhibition of purified neuronal NOS (nNOS) with an IC₅₀ value of 19.0 μM but showed little or no effects on inducible and endothelial NOS. Molecular docking simulations suggested an interaction between SU4312 and the haem group within the active centre of nNOS.

Conclusions and Implication

SU4312 exhibited neuroprotection against MPP⁺ at least partly via selective and direct inhibition of nNOS. Because SU4312 could reach the brain in rats, our study also offered a support for further development of SU4312 to treat neurodegenerative disorders, particularly those associated with NO-mediated neurotoxicity.     

纹状体中神经元活动的多巴胺调节

纹状体参与机体各种不同的行为活动 ,这些活动主要依赖于完整的多巴胺能神经支配 ,最近的电生理研究表明多巴胺通过改变电压依赖性的通道传导和突触传递来调节靶细胞的活动。该文对多巴胺如何调节纹状体神经元的活动作简要综述     

硫辛酸抗神经细胞老化的蛋白质组学分析

目的研究硫辛酸在神经细胞老化过程中对细胞保护作用的蛋白质分子基础。方法采用无血清培养神经母细胞瘤细胞方法建立实验性神经细胞老化模型。设立硫辛酸（IA）作用组和对照组,运用蛋白质组学技术平台,采用双向电泳结合基质辅助激光电离-飞行时间质谱技术分析,并鉴定表达受到硫辛酸调控的蛋白。结果经蛋白质组学技术分析,发现硫辛酸能阻止19个蛋白在老化过程中表达改变,成功鉴定出其中5个蛋白,其中STMN1、TPM4、SERB和PARK7在老化过程中表达下降,DLDH在老化过程中表达上升。结论硫辛酸抗老化保护神经细胞的作用机制涉及到对STMN1、TPM4、SERB、PARK7和DLDH等蛋白的调控。     

Adiponectin receptor signalling in the brain

Adiponectin is an important adipocyte-derived hormone that regulates metabolism of lipids and glucose, and its receptors (AdipoR1, AdipoR2, T-cadherin) appear to exert actions in peripheral tissues by activating the AMP-activated protein kinase, p38-MAPK, PPARα and NF-kappa B. Adiponectin has been shown to exert a wide range of biological functions that could elicit different effects, depending on the target organ and the biological milieu. There is substantial evidence to suggest that adiponectin receptors are expressed widely in the brain. Their expression has been detected in regions of the mouse hypothalamus, brainstem, cortical neurons and endothelial cells, as well as in whole brain and pituitary extracts. While there is now considerable evidence for the presence of adiponectin and its receptors in the brain, their precise roles in brain diseases still remain unclear. Only a few research studies have looked at this facet of adiponectins in brain disorders. This brief review will describe the evidence for important functions by adiponectin, its structure and known actions, evidence for expression of AdipoRs in the brain, their involvement in brain disorders and the therapeutic potential of agents that could modify AdipoR signalling.     

海洛因复吸对大鼠脑神经元的超微结构的影响

目的:建立海洛因复吸大鼠模型,观察海洛因复吸大鼠脑神经元的超微结构的变化。方法:将Wister大鼠随机分成正常组、复吸组。采用递增法人为给大鼠皮下注射(sc)海洛因造成动物成瘾。给予复吸组大鼠连续注射递增量海洛因8 d,为染毒成瘾。染毒后停止注射海洛因5 d,为戒断。按染毒→戒断的方法,周而复始反复3次建立海洛因复吸大鼠模型。给予正常组大鼠连续注射生理盐水8 d,停止注射生理盐水5 d为一个阶段,反复3次。在造模前、造模后各组大鼠进行体重测量;于实验d40,取大鼠前额叶皮质(PFC)、中脑腹侧被盖区(VTA)、伏隔核(NAc)部位脑组织,运用透射电镜观察大鼠脑神经元的超微结构。结果:造膜后12 h,复吸组与正常组比较,体重明显下降(P(0.01);正常组视野可见PFC、VTA、NAc各成分清晰,粗面内质网、核糖体、细胞核、核膜等结构基本正常;复吸组视野可见PFC、VTA、NAc神经元变性、肿胀等超微结构改变明显。结论:模仿人类吸毒成瘾,建立海洛因成瘾复吸大鼠模型稳定性、重复性好,适用于探讨复吸机制的实验研究。海洛因复吸大鼠相关脑区神经元超微结构损伤明显。     

Endothelin and post-ganglionic sympathetic neurons

1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post-ganglionic sympathetic neuronal development. 2. Endothelin is produced by post-ganglionic neurons and by cells adjacent to these neurons. 3. Post-ganglionic sympathetic neurons express functional receptors for ET. 4. Endothelin promotes the survival of cultured post-ganglionic sympathetic neurons and modulates the morphological and biochemical differentiation of these neurons. 5. Endothelin enhances the activity of nerve growth factor and modulates the release of neurotransmitter from post-ganglionic sympathetic nerve terminals.     

脑缺血中的细胞凋亡

凋亡和坏死是细胞死亡的两种主要方式,近期凋亡在脑缺血性细胞死亡中的作用逐步受到重视,这对近年来脑缺血中细胞凋亡的研究必有助益     

小胶质细胞与脑缺血关系的研究进展

小胶质细胞为脑内的主要免疫效应细胞, 参与一系列神经退行性疾病的发生。它的形态具有高度可塑性, 其形态学改变与其活化状态及生物学功能密切相关。脑缺血损伤后小胶质细胞发生活化, 且其活化受到精细调控。小胶质细胞在脑缺血损伤中发挥脑保护和神经毒性双相作用。因此, 深入研究小胶质细胞与脑缺血之间的关系, 以小胶质细胞的活化及调控作为出发点, 通过抑制小胶质细胞的过度活化、调控小胶质细胞表面或细胞内表达的受体或蛋白分子、拮抗小胶质细胞产生的神经毒性因子、促进小胶质细胞分泌神经保护性生物活性物质、阻断小胶质细胞介导的炎症反应等将为脑缺血的治疗提供新思路。本文对脑缺血损伤后, 小胶质细胞的活化及调控、效应及相关干预治疗等方面作一综述。