雌激素的神经保护机制研究进展

多种神经系统疾病如缺血性脑卒中、帕金森病 ( PD)、阿尔茨海默氏病 ( AD)等 ,发病率随年龄增加 ,并且显示出性别差异。近年来 ,许多研究提示雌激素的缺乏与这些疾病的发生、发展有关联 ,如果证明它们之间确实存在着因果关系 ,无疑能为疾病的预防和治疗提供新的途径。本文就雌激素提供神经保护的依据、可能的机制及雌激素替代治疗 ( ERT)的现状作一综述。1　“雌激素可能具有神经保护效应”假设的提出1 .1　流行病学调查以及病例对照研究结果　美国Framingham研究随访 2 0年发现 ,4 5～ 54岁年龄段的男性脑卒中年平均发病率 ( 2 0 / 1 0…     

白藜芦醇抗氧化作用在神经保护中的研究进展

白藜芦醇是一种含有菧类结构的非黄酮类多酚化合物,具有抗肿瘤、保护心血管、抗菌、抗病毒、免疫调节等多种生物活性和药理作用,对神经系统也有多种保护机制,其中抗氧化清除自由基的作用受到广泛关注,深入研究白藜芦醇抗氧化作用具有重要临床意义,本文就其抗氧化作用在神经保护中的研究进展做一综述。     

阿托伐他汀钙在急性脑梗死中的神经保护作用

正随着我国老龄化现象日益加重,心脑血管患者越来越多,急性脑梗死是神经内科常见疾病,致残率高,严重威胁患者的生命健康。急性脑梗死造成梗死区神经组织的损伤,且梗死后导致的脑水肿及氧化应激反应会进一步造成神经损伤,从而严重影响患者神经功能及日后生活质量[1]。最新研究表明[2],炎症反应在脑缺血损伤中起重要作用,炎症反应是脑梗死的诱导因素,促进疾病的发生与发展。研究表     

视神经损伤后睫状神经营养因子的神经保护效应

目的 研究睫状神经营养因子(CNTF)不同给药途径对猫视神经不全损伤后的神经保护效应.方法 完成猫视神经不全损伤模型的制作;实验组和空白对照组分别给予静脉、前房、玻璃体内CNTF注射和生理盐水玻璃体注射;术后15 d双侧上丘、外侧膝状体显微注射DiI逆行神经示踪;不同时间点行视觉诱发电位(PVEP)检测;术后30 d原位心脏灌注;视网膜铺片,视网膜神经节细胞计数;取术侧视神经组织,光镜和电镜观察各组视神经形态变化.结果 空白对照组术侧眼PVEPP100较实验各组振幅明显减低,潜伏期明显延长,差异有统计学意义(P＜0.01);与空白对照组比较,实验组视网膜神经节细胞存活数量明显增加(P＜0.01),神经结构更加完整.结论 视神经不全损伤后CNTF不同途径给药具有视神经保护效应,但效应存在差异.

Abstract：

Objective To research the nerve protective effect of ciliary neurotrophic factor (CNTF) after cat optic nerve not entire injury.Methods Completes the cat optic nerve not entire damage model.The experimental group gives CNTF by in the vein,the anterior chambe,the intravitreal to inject separately,the control group gives the physiological saline.Operation latter 15 days of two-sided anterior colliculi,lateral geniculate body microinjection DiI retrogradation nerve tracing.The different time spot completes the examination of visual evoked potential (PVEP).Operation latter 30 days complete the situ heart dabbling;Retina stretched preparation,retina ganglion cell counting.Takes the optic nerve of operation side,the light microscope and the electron microscope observation morphologic change of optic nerve.Result Controlled group PVEP compares the experimental groups oscillation amplitude of P100 to decrease obviously,incubation period of P100 obvious extension,difference remarkable (P ＜ 0.0l ).Compares with the controlled group,the survival number of retina ganglion cell of experimental groups increases obviously(P＜0.01 ),the nerve structure is more complete.Conclusion After optic nerve not entire damage,the CNTF different way injection has the optic nerve protective effect,but effect existence difference.     

雌激素对雄性大鼠缺血性脑损伤的神经保护作用及其可能机制

目的 探讨雌激素对雄性大鼠局灶性脑缺血的神经保护作用及其可能机制。方法 随机将大鼠分为雌激素预处理组、雌激素＋他莫昔芬预处理组和对照组，采用线栓法制作大鼠大脑中动脉闭塞（MCAO）模型，观察缺血后2h和24h脑梗死体积、大鼠死亡率、神经功能缺损程度、神经元凋亡以及Bcl-2、Bax、p53蛋白的表达。结果 缺血后2h和24h，雌激素预处理组较对照组脑梗死体积小、死亡率低、神经功能缺损程度轻、神经元凋亡少，并抑制Bax、p53表达，促进Bcl-2蛋白表达。雌激素受体拮抗剂他莫昔芬可抑制这一作用。结论 雌激素对雄性大鼠缺血性脑损伤具有明显的神经保护作用。对基因和非基因因素的影响是神经保护作用的可能机制。     

脑源性神经营养因子在中枢神经系统损伤中的多种神经保护作用及其机制的研究进展

中枢神经系统损伤后脑源性神经营养因子（BDNF）可以通过多种机制发挥其神经保护作用,如抑制神经元及少突胶质细胞的凋亡,促进神经突触的生长和轴突再生,促进髓鞘再生,以及调节损伤后的免疫反应和神经兴奋性等。本文主要综述了BDNF在神经保护中可能的分子机制,以进一步明确其在神经治疗中的应用价值。     

植物雌激素对去势雌性大鼠缺血性脑损伤的神经保护作用

目的对比研究植物雌激素和动物雌激素对去势雌性SD大鼠永久性局灶性脑缺血组织的神经保护作用。方法采用线栓法建立右侧永久性大脑中动脉阻断模型。缺血24h后立即断头取脑,冠状切片,HE染色后于光镜下观察缺血侧大脑皮层的病理变化,应用免疫组化法检测不同实验组大鼠缺血侧Cfos表达情况,以DNA缺口末端标记法原位检测细胞凋亡,通过TTC染色比较脑梗死体积百分比。结果动物雌激素(17β雌二醇)组及植物雌激素(葛根素)组与生理盐水组相比,光镜下正常神经细胞密度显著增加,缺血侧C-fos表达阳性的细胞数明显减少,凋亡细胞数显著减少,脑梗死体积百分比也明显缩小(P<0.05)。两种雌激素相比,上述4项指标差异均无显著性(P>0.05)。结论两种雌激素对缺血性脑损伤均有保护作用,可减弱大脑缺血梗死灶边缘区的Cfos表达,从而延缓神经细胞凋亡。这可能是雌激素脑保护作用的机制之一。     

葡萄糖转运蛋白-3及缺氧诱导因子1α在星形细胞瘤中的表达

目的 探讨葡萄糖转运蛋白-3(GLUT-3)和缺氧诱导因子(HIF)-1α在星形细胞瘤中的表达及其临床意义.方法 应用免疫组化染色和RT-PCR方法检测80例星形细胞瘤患者肿瘤组织中GLUT-3和HIF-1α表达情况,另取10例星形细胞瘤周围做内减压切除的正常脑组织为对照.结果 GLUT-3在Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞瘤中阳性表达率分别为35%、60%、80%、100%,HIF-1α在Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞瘤中阳性表达率分别为20%、50%、75%、95%,两者呈正相关关系(r=0.550,P=0.000).GLUT-3 mRNA表达在Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞瘤中分别为0.19±0.03、0.45±0.12、0.67±0.11、0.89±0.19,HIF-1α mRNA在Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞瘤中分别为0.21±0.06、0.48±0.11、0.72±0.16、0.93±0.12,各级别间比较差异均有统计学意义(P=0.000),且GLUT-3 mRNA、HIF-1αmRNA表达强度与星形细胞瘤的病理分级呈正相关关系(r=0.887,P=0.000;r=0.813,P=0.000),二者之间也呈正相关关系(r=0.530,P＜0.05).结论 GLUT-3与HIF-1α表达强度和星形细胞瘤的病理分级成正相关,可以作为判断星形细胞瘤生物学行为的重要指标.

Abstract：

Objective To explore the expressions and clinical significances of glucose transporter protein-3 (GLUT-3) and hypoxia-inducible factor-1α (HIF-1α) in astrocytoma. Methods The astrocytoma tissues from 80 patients with astrocytoma were chosen as experimental group; and the normal cerebral tissues from another 10 patients performed depression around the astrocytoma were chosen as control group. Immunohistochemistry and RT-PCR were employed to detect the GLUT-3 and HIF-1α expressions in these tissues. Results The protein of GLUT-3 in grade Ⅰ, grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were positively expressed, respectively, as 35%, 60%, 80% and 100% by immunohistochemistry; the protein of HIF-1α in grade Ⅰ, grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were positively expressed, respectively, as 20%, 50%, 75% and 95% by immunohistochemistry; positive correlation was noted between the protein levels of GLUT-3 and HIF-1α (r=0.550, P=0.000). The mRNA levels of GLUT-3 in grade Ⅰ, grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were expressed, respectively,as 0.19±0.03, 0.45±0.12, 0.67±0.11 and 0.89±0.19 by RT-PCR; the mRNA levels of HIF-1α were expressed, respectively, as 0.21 ±0.06, 0.48±0.11, 0.72±0.16 and 0.93±0.12 by RT-PCR; and the mRNA expression level of GLUT-3 were positively correlated to that of HIF-1α (r=0.530, P=0.000).Significant difference between each 2 different pathological grades of astrocytoma was noted (P＜0.05). The mRNA expression levels of GLUT-3 and HIF-1α were positively correlated to the pathological grades of astrocytomas (r=0.887, P=0.000; r=0.813, P=0.000). Conclusion The expression of GLUT-3 and HIF-1α in astrocytoma are significantly correlated to tumors' pathology grade, which can be taken as a useful marker for predicting the biological behavior.     

阿托伐他汀预先干预对急性脑梗死患者的神经保护作用

目的 探讨阿托伐他汀预先干预对急性脑梗死的神经保护作用.方法 80例急性脑梗死患者按照就诊前3个月是否服用阿托伐他汀钙为他汀组40例和对照组40例,入院后对照组给予常规治疗,而不用他汀类药物,他汀组在对照组治疗的基础上继续口服阿托伐他汀.均在发病72 h时比较2组患者:(1)生化检测指标:血浆超敏C反应蛋白(hs-CR...     

胰岛素样生长因子-1神经保护作用的研究进展

胰岛素样生长因子－1（Insulin-like growth factor-1，IGF-1）是一种与机体组织分化、增殖和成熟有关的重要细胞因子。IGF-1与其受体结合具有促进细胞分化增殖、抑制凋亡和类胰岛素的代谢作用，并还可能与其他神经营养因子协同发挥神经保护作用。其中，IGF-1保护缺血性脑损伤的可能机制有：甘氨酸-脯氨酸-谷氨酸（glycine-proline-glutamate，GPE）对神经细胞的保护作用、抗凋亡作用、阻止L型钙通道的开放、对一氧化氮合酶（NOS）的双重作用以及对抗兴奋性氨基酸的毒性等。随着临床实验的开展，IGF-1有可能作为脑保护剂用于缺血性脑损伤的治疗。     

Outlook on the neuroprotective effect of estrogen

<正>Epidemiologic studies often consider gender differences in a particular pathology,and constantly observe variations between men and women.Indeed,a remarkable sexual dimorphism exists in the epidemiology of neurological conditions and brain diseases.Physiologically,males and females differ by their levels of circulating hormones that drive     

Molecular and biochemical aspects of the neuroprotective effect of the selective estrogen receptor modulator tamoxifen in a model of acute cerebral ischemia

We studied the neurochemical aspects of the neuroprotective action of a selective modulator of the estrogen receptors, tamoxifen citrate, in a model of acute cerebral ischemia (ACI). It was shown that modeling of cerebral ischemia is followed by pathobiochemical changes in the brain tissue: a rapid shift of thioldisulfide homeostasis, intensification of free radical oxidation, and impaired synthesis of the cytoprotective protein Hsp70. A course of the 1 mg/kg tamoxifen citrate led to the normalization of the thiol-disulfide system due to an increase of the glutathione level in the brain tissue which, in turn, restricted the development of oxidative and nitrosative stress. In addition, Western blot analysis showed that treatment with tamoxifen citrate increased the Hsp70 level in the brain tissue, which resulted from genomic and non-genomic actions. The neuroprotective profile of tamoxifen citrate that we found here opens the future perspective of the studies in this field for introduction of this agent as a neuroprotective drug into clinical practice.     

Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus

Although estrogen has beneficial actions in brain, recent clinical trials demonstrated adverse neural effects of hormone therapy in postmenopausal women. The cause(s) of this disconnect between experimental and clinical findings may include unanticipated effects of progestins. We report that both natural progesterone and the clinical progestin medroxyprogesterone acetate block estrogen neuroprotection. These findings underscore the need to evaluate neural actions of progestins in the rational design of hormone therapy.     

The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury

Objective

Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.

Methods

Locomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.

Results

Basso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).

Conclusion

VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.     

Differences in dopaminergic neuroprotective effects of estrogen during estrous cycle

Previous studies suggest that estrogen treatment protects nigrostriatal dopaminergic neurons, but have not examined whether the changes in estrogen levels during estrous cycle can influence the susceptibility of these neurons to neurotoxins. Here we show that the loss of dopaminergic neurons in the substantia nigra was greater in animals lesioned at diestrus (low estrogen) using 6-hydroxydopamine or buffered iron chloride, when compared with animals lesioned at proestrus (high estrogen). Lesioning at diestrus with 6-hydroxydopamine reduced the striatal dopamine content, whereas the dopamine content was preserved in animals lesioned at proestrus. The density of the dopamine transporter, upon which 6-hydroxydopamine toxicity is dependent, was lower when circulating estrogen was high. These results thus support a neuroprotectory role for estrogen.     

Other neuroprotective therapies on trial in acute stroke

New neuroprotective agents on trial may potentially offer benefit to stroke patients without the associated hemorrhagic risk of thrombolytic therapy. Clinical investigation of these drugs has been designed to obtain the highest probability of success, or concentrates on the salvageable ischemic brain and use infarct growth on MRI as a surrogate end-point. Nine substances in 10 trials are currently being tested in three therapeutical strategies in patients with acute ischemic stroke. These strategies focus on: (1) the optimal management of serum glucose with the infusion of glucose, insulin and potassium to induce and maintain euglycemia; (2) the modulation of the inflammatory response with recombinant human interferon-beta(1a), and (3) interfering with the ischemic cascade using magnesium, albumin, the metal iron chelator DP-b99, the AMPA receptor antagonist zonampanel, the serotonin agonists repinotan and piclozotan, the free radical scavenger cerovive, and the membrane modulator citicoline. Future directions should develop neuroprotective compounds that are safe and well tolerated, are effective in a broad range of patients and can be used with or without rt-PA.     

神经节苷脂对活体实验性缺血再灌注鼠脑损伤的磁共振成像与波谱研究

目的研究神经节苷脂对活体实验性脑梗死大鼠脑组织氮-乙酰天门冬氨酸(NAA)及乳酸(Lac)等代谢产物的影响。方法采用磁共振成像与波谱技术原位动态观察神经节苷脂对活体鼠脑组织损害程度、神经递质方面的影响。分别对缺血再灌注组及神经节苷脂治疗组鼠脑组织缺血、水肿及氮-乙酰天门冬氨酸(NAA)与乳酸(Lac)等代谢产物变化进行观察和比较。结果在缺血60min再灌注1h、3h、6h神经节苷脂均能减小高信号区的体积,有效减少脑缺血后Lac/(PCr Cr)比值的上升和NAA/(PCr Cr)比值的下降,与缺血再灌组相比较有显著差异(P<0.01)。结论神经节苷脂具有显著的缺血后脑保护作用,磁共振成像与波谱技术可为缺血再灌注后神经脑保护剂作用机制的研究提供精确的神经影像学信息。     

TIA对后继脑梗死神经保护作用的临床研究

目的探讨预先短暂性脑缺血发作(TIA)是否对后继脑梗死具有神经保护作用。方法根据脑梗死患者是否预先发生同侧的TIA分为TIA组和无TIA组,分别从TIA持续时间、发作次数、与脑梗死间隔时间及梗死部位几方面同无TIA组比较,采用ADL评分标准,评定患者预后恢复情况。结果Ⅰ级预后预先有TIA的占72%,无TIA的占63%,二者相比差异无显著性(X~2=3．31,P＞0．05)。但脑梗死前有TIA且持续时间在5～20min、发作次数2～3次,与脑梗死间隔不超过1周者,其Ⅰ级预后较多,同无TIA组相比较差异有显著性(P＜0．05)。结论脑梗死前发生的TIA有可能对人脑产生缺血耐受作用。TIA的神经保护性与其发作持续时间、发作次数及与脑梗死间隔时间有一定关系。     

柚皮素神经保护作用的研究进展

据研究,柚皮素来源广泛,具有多重药物作用,本文综述了柚皮素在神经系统疾病中发挥脑神经保护作用的机制,将近几年来的国内外文献进行整理及分析,为后续柚皮素的开发研究及临床运用提供参考数据。     

急性缺血性脑卒中的神经保护治疗

脑卒中是影响人类健康的主要疾病之一,为我国城市人口死亡的首位原因。约三分之一的脑卒中幸存者残留不同程度的神经功能障碍。急性缺血性脑卒中治疗的最重要途径为改善脑血流(溶栓)和阻断神经元缺血性病理生化级联反应,即神经保护治疗。一、神经保护治疗的合理性脑梗死的发生取决于两个基本条件,即脑血流量(cerebralbloodflow,CBF)下降的严重程度和缺血持续的时间。脑缺血后,若脑循环在一段时间内恢复,脑功能可获完全恢复,该时间为“再灌注时间窗”。由于脑缺血后引起的病理生理变化持续存在,即使重新建立起足够的脑循环,仍可能产生延迟…