雌激素抗神经细胞凋亡的相关因子

雌激素是一种类固醇性激素,主要生理功能是促进女性生殖系统各个器官的发育和维持女性的第二性征。然而,越来越多的研究发现,雌激素还具有抗神经细胞凋亡的作用。雌激素抗神经细胞凋亡与其作用于下列多种因子有关,如Bcl-2家族、Ca^2＋、胱天蛋白酶（caspase）家族,以及胰岛素样生长因子-驳取？     

葛根素对帕金森病细胞模型的保护作用研究

目的:研究葛根素对帕金森病细胞模型的保护作用及其具体的作用机理.方法:用0.16mM的MPP+处理PC12细胞48h建立帕金森病细胞模型.实验分为对照组、损伤组和保护组,损伤组用MPP+(0.16mM)处理PC12细胞;保护组用葛根素提前预处理PC12细胞1h,后加MPP+.检测PC12细胞存活率、Caspase-3活性及ERβ的转录活性.结果:葛根素能够抑制caspase-3的激活,且其依赖于ERβ的表达,雌激素受体拮抗剂ICI182,780可阻断上述效应;其次葛根素可提高ERβ的转录活性.结论:葛根素对MPP+诱导损伤的PC12细胞具有抗细胞凋亡的保护作用,且具体的作用机理可能依赖于ERβ介导的经典的基因组作用模式.     

葛根素对糖尿病视网膜细胞凋亡作用的研究进展

糖尿病的发病率逐年上升,其并发症的严重性日趋明显,特别是糖尿病视网膜病变导致视力下降和丧失已经引起了广泛关注,所以研究糖尿病视网膜病变的发病机制及其防治是必要的。糖尿病视网膜病变是一种多种机制共同作用的复杂性疾病,而细胞凋亡在糖尿病视网膜病变的发生和发展中起着重要的作用,所以研究细胞凋亡对糖尿病视网膜病变的治疗有着重要意义。由于细胞凋亡研究的深入,人们将注意力集中于糖尿病视网膜细胞凋亡能否得到抑制和逆转的问题上。研究发现,糖尿病视网膜病变细胞凋亡可能与视网膜新生血管形成、VEGF水平增高等因素有关。当前对葛根素的研究表明,葛根素能有效抑制视网膜新生血管形成,并且对于缺血、缺氧等因素引起的损害有很强的改善作用,葛根素还可以降低糖尿病糖基化终产物水平,甚至对视网膜超微结构的损害具有一定的保护作用,所以葛根素可能是治疗糖尿病性视网膜病变的新策略。本文就近期糖尿病视网膜病变中细胞凋亡的有关研究和葛根素的抗细胞凋亡作用做一综述,提示在糖尿病视网膜病变中葛根素的不可忽视的作用。     

科学家发现能有效保护脑神经细胞的植物

一个日美联合科研小组最近发现，一种名为迷迭香的常绿灌木中富含鼠尾草酸，它具有保护脑神经细胞的功效，迷迭香因此有望用于研制预防阿尔茨海默氏症的药物。     

葛根素对大鼠肝脏缺血再灌注损伤的保护作用

目的:观察葛根素预处理时大鼠肝脏缺血再灌注损伤的保护作用.方法:雄性SD大鼠,建立肝脏缺血再灌注模型(HIR).随机分为假手术组、HIR组和HIR-葛根素预处理组.分析各组动物血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)及乳酸脱氢酶(LDH)含量的变化,观察肝组织病理学的改变.结果:肝脏缺血再灌注损伤后,与假手术组比较,血清中AST、ALT、LDH含量均显著增加,同时肝脏门静脉周围瘀血明显,可见少量散在的肝细胞片状坏死灶,有少量炎性细胞和单核细胞浸润,肝细胞肿胀、脂肪空泡变性、核浓缩;经40mg/kg剂量的葛根素预处理7天后,与模型组相比,血清中AST、ALT、LDH均显著降低,肝脏的瘀血明显较模型组轻,肝小叶结构基本正常,微血管未见明显损伤,窦间隙稍宽,细胞变性坏死不明显,偶见少量肝细胞坏死.结论:葛根素预处理对大鼠缺血再灌注肝脏损伤有一定的保护作用.     

绞股蓝多糖的分离纯化及其对神经细胞谷氨酸损伤的保护作用

本文对绞股蓝Gyrugstemma pentaphyllum(Thunb.)Makino(GP)中的多糖成分进行了分离纯化,得到了两个均一多糖:GPS-2和GPS-3,并对GPS-3进行了纯度分析、分子量测定,结果表明:GPS-3的糖含量为78.10%,分子量为9100 Dal.然后在细胞水平研究了这两种多糖对神经细胞谷氨酸损伤的保护作用.结果显示,不同浓度绞股蓝多糖试验组神经细胞损伤有不同程度的减轻,与谷氨酸损伤组相比有显著性差异(P＜0.01).     

Ghrelin在应激状态下对机体保护作用的研究进展

Ghrelin是一种胃分泌素,具有多种生物学作用,对机体的功能发挥广泛的影响。近几年的研究发现,在病理状态下,Ghrelin对机体多个器官系统可发挥保护作用。本文从应激的这一角度出发,对10年来Ghrelin在应激状态下对机体各个器官系统的保护作用做一综述。     

葛根素对糖尿病致肺损伤的保护作用及其机制的研究

目的:探讨糖尿病对肺脏损伤及葛根素对肺组织影响的可能机制。方法:腹腔注射链脲佐菌素(STZ)建立大鼠糖尿病(DM)模型,SD大鼠随机分为对照组(C组)、糖尿病组(DM组)、糖尿病 葛根素组(DM Pur组)。检测注药前及模型成立后第20d、40d、60d的血糖及体重的改变。检测肺组织中一氧化氮(NO)和丙二醛(MDA)的含量、超氧化物歧化酶(SOD)活性。结合光镜、电镜、免疫组织化学染色方法综合评价。结果:①DM组NO、MDA高于C组(P<0.01),SOD活性低于C组(P<0.01),DM Pur组NO含量明显低于DM组(P<0.01),MDA含量40d开始显著降低(P<0.01),SOD活性高于DM组(P<0.01)。②光镜下见肺泡隔增厚,炎性细胞浸润;电镜下见Ⅱ型肺泡上皮细胞微绒毛数量明显减少,嗜锇性板层小体数量明显减少,细胞间质胶原纤维增生,葛根素可减轻肺组织上述病理性改变。③免疫组织化学染色结果:DM组细胞胞质中可见ONOO-特征性代表物硝基酪氨酸(ni-trotyrosine,NT)黄染阳性信号表达,且较对照组略为增强,DM Pur组黄染信号较DM组略为减弱。结论:①DM时可发生肺组织损伤,可能与长期高血糖诱导产生大量自由基有关。②NO/ONOO-通路是DM造成肺组织细胞损伤的机制之一。③初步证实葛根素能在一定程度上抑制高血糖诱导肺组织中自由基的过量生成,降低肺组织中的ONOO-的过度表达,这可能是其抗DM时肺组织损伤的作用机制之一。     

灵芝属多糖对肾上腺酮诱导神经细胞凋亡的保护作用

[目的]筛选和评价灵芝属多糖对肾上腺酮(CORT)诱导神经损伤的保护作用,为灵芝在抗抑郁功能方面的开发奠定基础。[方法]以CORT诱发神经细胞发生损伤后给予灵芝属多糖提取物,分别通过MTT法、乳酸脱氢酶(LDH)胞外释放法、总DNA定量分析法以及荧光标记法确定细胞毒性以及对损伤细胞的保护作用。[结果]结果显示灵芝属多糖在低作用浓度下对PC12细胞不具有毒性,在100μg/mL的作用浓度下灵芝孢子粉多糖(PGL)可以显著提高损伤细胞存活率的比例为22%,减少LDH的释放比例为11.08%,增加胞内总DNA含量14.65%,是所有待测多糖中作用最佳的。[结论]PGL对细胞具有低毒的特点,显著改善CORT对细胞的损伤作用,具有明显的神经保护作用,可作为抗抑郁药物进行研究和开发。     

壳寡糖对神经细胞的抗氧化保护作用研究

神经细胞发生氧化损伤是导致阿尔茨海默病等神经退行性疾病的重要原因之一。为探讨壳寡糖(chitosan oligosaccharide,COS)对神经细胞的保护机制,首先采用过氧化氢(hydrogen peroxide,H_2O_2)建立SH-SY5Y神经细胞氧化损伤模型,随后通过细胞存活率(MTT法)、丙二醛(MDA)含量、乳酸脱氢酶(LDH)释放量、Hoechst33342荧光染色法、流式细胞术研究各组细胞凋亡情况,并用Western-blot检测相关蛋白质的表达水平,从而分析COS对H_2O_2所致神经细胞氧化损伤的影响。研究发现,H_2O_2能明显诱导SH-SY5Y细胞损伤,而COS可抑制H_2O_2引起的细胞死亡,表现为神经细胞存活率升高、LDH释放量及MDA含量下降;且对H_2O_2所致细胞凋亡具有明显的抑制作用,凋亡蛋白Bax和抗凋亡蛋白Bcl-2的比值下降。上述结果提示COS保护机制可能与其抗氧化、减轻脂质过氧化损伤以及抑制细胞凋亡有关。     

The effects of interferon-γ on the central nervous system

Interferon-gamma (IFN-γ) is a pleotropic cytokine released by T-lymphocytes and natural killer cells. Normally, these cells do not traverse the blood-brain barrier at appreciable levels and, as such, IFN-γ is generally undetectable within the central nervous system (CNS). Nevertheless, in response to CNS infections, as well as during certain disorders in which the CNS is affected, T-cell traffic across the blood-brain barrier increases considerably, thereby exposing neuronal and glial cells to the potent effects of IFN-γ. A large portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-γ plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical and physiological effects of IFN-γ are discussed in the context of the potential consequences of such activities on the developing and mature nervous systems.     

Regeneration of the central nervous system using endogenous repair mechanisms

Recent advances in developmental and stem cell biology have made regeneration-based therapies feasible as therapeutic strategies for patients with damaged central nervous systems (CNSs), including those with spinal cord injuries, Parkinson disease, or stroke. These strategies can be classified into two approaches: (i) the replenishment of lost neural cells and (ii) the induction of axonal regeneration. The first approach includes the activation of endogenous neural stem cells (NSCs) in the adult CNS and cell transplantation therapy. Endogenous NSCs have been shown to give rise to new neurons after insults, including ischemia, have been sustained; this form of neurogenesis followed by the migration and functional maturation of neuronal cells, as well as the responses of glial cells and the vascular system play crucial roles in endogenous repair mechanisms in damaged CNS tissue. In this review, we will summarize the recent advances in regeneration-based therapeutic approaches using endogenous NSCs, including the results of our own collaborative groups.     

Exploring adverse effects of puerarin on catalase by multiple spectroscopic investigations and docking studies in vitro

Puerarin belongs to one of the most familiar tradition medicines of China, but adverse effects of puerarin during the clinical treatment have been found for years, the mechanisms of which remain unclear. In this study, toxic mechanisms of puerarin on the structure and function of catalase were studied by multiple spectroscopic techniques, isothermal titration calorimetric measurement, and molecular docking methods in vitro. Results showed puerarin could inhibit the activity of catalase due to direct interactions between puerarin and catalase, resulting in conformational and functional changes of the enzyme. To be specific, puerarin statically quenched catalase fluorescence, bound into the active site channel of catalase, hindered the path of the catalytic substrate (H₂O₂), affected its skeleton conformation and secondary structure, and interacted with the enzymatically related residues through hydrophobic interactions (ΔH > 0 and ΔS > 0) spontaneously (ΔG < 0). This study illustrates potential adverse effects of puerarin, which should catch more attentions during the clinical diagnosis.     

Evolution of a neuroprotective function of central nervous system myelin

The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to mouse PNS myelin, where P0 is the major structural protein today. The PLP-P0 shift resulted in reduced myelin internode length, degeneration of myelinated axons, severe neurological disability, and a 50% reduction in lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal lifespan and no axonal degeneration. These data support the hypothesis that the P0-PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia.     

Cell fate control in the developing central nervous system

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases.     

Protective roles of melatonin in central nervous system diseases by regulation of neural stem cells

Neural stem cells (NSCs) are immature precursors of the central nervous system (CNS), with self‐renewal and multipotential differentiation abilities. Their proliferation and differentiation are dynamically regulated by hormonal and local factors. Alteration in neurogenesis is associated with many neurological disorders. Increasing evidence suggests that modulation of NSCs can be a promising therapeutic approach for neural injury and neurodegenerative disorders. Melatonin, a pineal gland‐derived hormone, regulates the neuroimmuno‐endocrine axis and is functionally important to the circadian rhythm, tumour suppression and immunity. In the CNS, melatonin exerts neuroprotective effects in many diseases, such as Parkinson's disease, Alzheimer's disease and ischaemic brain injury. Emerging evidence suggests that it might also mediate such protective action by influencing proliferation and differentiation of NSCs. In this article, we review the current literature concerned with effects of melatonin on NSCs in different physiological and pathological conditions.     

Selected clinical research involving the central nervous system

This paper updates three clinical research projects involving the central nervous system. Discussions of conditions with encephalocele include several associations: encephalocele/craniostenosis, transsphenoidal encephalocele/hypothalamic-pituitary dysfunction, encephalocele/oculo-auriculo-vertebral spectrum, and encephalocele/frontonasal dysplasia. The relationship between oculo-auriculo-vetebral spectrum with encephalocele and frontonasal dysplasia with epibulbar dermoids and ear tags is also discussed and an explanation for encephalocele formation in the Apert syndrome is provided. Studies of the central nervous system in Apert syndrome indicate that distortion ventriculomegaly is common, but progressive hydrocephalus occurs infrequently. A recurrent pattern of abnormalities was discerned consisting of megalencephaly, gyral abnormalities, and defects of the corpus callosum and limbic structures. Five neuropathologic studies lend further support to this pattern of CNS anomalies in the Apert syndrome. In a study of holoprosencephaly, eight principles governing associated facial dysmorphism were derived. Each diagnostic category was shown to have its own frequency and range of holoprosencephalic faces. Some categories, such as del(13q), have narrow ranges; others, such as trisomy 13 syndrome, have broad ranges. However, no broad diagnostic range is known to include agnathia-holoprosencephaly and other severe forms of facial dysmorphism without agnathia. Absent maxillary incisors and a single maxillary central incisor are extremely common in holoprosencephaly with severe facial dysmorphism and may occur on occasion as a striking microform of holoprosencephaly, most commonly in the autosomal dominant form.     

Motor effects of serotonin in the central nervous system

Serotoneric pathways in the CNS affect posture and movement, as well as behavioral responses to arousing stimuli. Pharmacologic analysis of these effects has led to an increasingly complex and confusing literature. Increased availability of serotonin (5-HT) by administration of precursors, or by its direct intracranial infusion can induce inhibitory or excitatory behavioral effects depending on the conditions of the experiment, although generally motor inhibition has been found. Availability of 5-HT has been decreased by electrolytic lesions of the raphe nuclei, inhibition of tryptophan hydroxylase, or use of selective neurotoxins. These treatments have generally increased motor activity, especially spontaneous locomotion in a familiar environment, as well as sexual or aggressive behaviors; other behaviors, such as responses in a novel environment, presumably associated with curiosity or fear, have been paradoxically decreased after loss of 5-HT. This differentiation may occur to an important extent through 5-HT projections to hippocampus and limbic structures, notably from the median raphe. Increases or decreases of brain 5-HT, respectively, generally tend to decrease and increase responses to catecholamine agonists such as amphetamines, and some effects of 5-HT may be mediated through catecholaminergic systems. Increased availability of 5-HT in the presence of MAO inhibitors, or challenge with 5-HT-agonists after selective 5-HT-denervation in the CNS has led to a behavioral syndrome marked by hyperactivity, autonomic arousal and myoclonic seizures. The mechanisms underlying this complex response may be mediated by descending 5-HT systems that result in motor excitation at the spinal cord level, in contrast to rostral projections to forebrain that may mediate many behaviorally inhibitory responses.