水通道蛋白AQP9在帕金森病脑组织中的表达及作用

目的观察大鼠帕金森病(Parkinson’disease,PD)水通道蛋白9(aquaporin 9,AQP9)在脑组织中的表达变化,研究AQP9在帕金森病脑组织发病机制中的作用。方法制造帕金森病动物模型,应用HE染色、免疫组织化学、RT-PCR等方法观察大鼠脑组织AQP9表达变化。结果免疫组织化学和RT-PCR检测结果显示,帕金森病组脑组织AQP9和AQP9mRNA的表达呈动态变化过程,帕金森病组大鼠术后各时间点(除外术后2周时间点)在鼠左侧黑质致密部(SNC)及中脑腹侧被盖区(VTA)区AQP9和AQP9mRNA表达均比假手术组高。结论高表达的AQP9,可能通过调节水电解质与能量代谢,从而在帕金森病发病机制中起重要作用。     

水通道蛋白在外伤性脑水肿中的作用

本文介绍了水通道蛋白(Aquaporin,AQP)的分类与分布以及 AQP4调节的最新研究结果。MAPKs 信号通路可能参与 AQP4的表达调节,alpha-syntrophin 可能参与 AQP4的定位调控。总结归纳了 AQP4在外伤性脑水肿中的作用,指出 AQP4可能起到促进外伤性脑水肿形成及消散的双重作用。     

水通道蛋白1在人成血管母细胞瘤中的表达与分布变化

目的 探讨人成血管母细胞瘤水通道蛋白I(AQP1)的表达变化在肿瘤发展过程中的病理生理意义. 方法 将自1980年至2005年我科收治的26例成血管母细胞瘤患者分为两组:实体肿瘤组与囊性肿瘤组,采用免疫组织化学方法 检测AQPl在成血管母细胞瘤的表达状况,RT-PCR方法 分析成血管母细胞瘤AQP1 mRNA的表达水平变化,激光共聚焦显微镜研究AQP1在血管内皮细胞及肿瘤细胞的表达分布关系.运用Western blot杂交分析AQP1蛋白在成血管母细胞瘤中的表达水平变化. 结果 免疫组织化学结果 显示,与正常脑组织相比,AQP1在成血管母细胞瘤中的表达水平明显升高,差异有统计学意义(P=0.002).在囊性成血管母细胞瘤中,AQP1的表达主要分布在肿瘤间质细胞膜上.在55.6%的实体成血管母细胞瘤中,肿瘤微血管内皮细胞上有AQP1的表达.仅44.4%的实体成血管母细胞瘤肿瘤间质细胞膜上有AQP1的表达.RT-PCR与Western blot杂交分析均表明.成血管母细胞瘤中AQP1 mRNA和蛋白的表达水平升高,且囊性成血管母细胞瘤中AOP1 mRNA和蛋白的表达水平明显高于实体性成血管母细胞瘤. 结论 AQP1表达的异常可能参与了人成血管母细胞瘤的形成与发展过程.同时,AQP1表达、分布的异常可能是人成血管母细胞瘤中瘤囊的形成与发展的重要病理生理机制.     

水通道蛋白与中枢神经系统疾病

水通道蛋白(aquaporins,AQPs)是近年来发现的一组参与跨细胞水转运的膜通道蛋白家族,在中枢神经系统(CNS)内分布广泛,在维护脑内渗透压及水电解质平衡、脑脊液分泌及平衡,以及在脑水肿发生过程中发挥关键作用。本文对水通道蛋白在中枢神经系统的分布、生理学意义及在神经系统疾病中的意义进行了综述。1水通道蛋白的发现与分类1988年Peter Agre[1]发现了第一种水通道蛋白,他在红细胞膜上发现一种分子量为28kDa的水通道结合膜蛋白(CHIP28),并将其成功地转染到非洲爪蟾卵母细胞,结果显示其具有选择性水通透的功能,CHIP28即为后来的AQP1…     

实验性脑出血后水通道蛋白-4的表达变化

目的　研究出血性脑水肿病理过程中水通道蛋白 4 (aquaporin 4 ,AQP4 )的表达与脑水肿形成之间的关系。方法　采用胶原酶制作大鼠脑出血模型 ,原位杂交和免疫组化法检测AQP4mRNA和蛋白质的表达变化 ,并用电镜技术和微血管灌注法观察脑水肿区的超微结构和微血管的变化。结果　与对照组相比 ,脑出血后 6h ,AQP4mRNA和蛋白质在脑水肿区表达增强 ,AQP4mRNA(吸光度值 ,A)由 0 2 9上升到 0 5 7(P <0 0 1) ,AQP4蛋白A值由 0 0 6上升到 0 15 (P <0 0 1) ,电镜下可见脑组织轻度水肿 ;至 72h ,AQP4mRNA和蛋白质的表达达到高峰 ,AQP4mRNA的A值为 0 88,AQP4蛋白A值为 0 2 5 ,此时脑组织严重水肿 ,神经元、胶质细胞和内皮细胞明显肿胀 ,毛细血管造影可见毛细血管开始增生 ;第 7天 ,AQP4的表达已减少 (尤以mRNA明显 ) ,但仍显著高于对照组 ,此时脑水肿已减轻。在整个脑水肿的形成过程中 ,AQP4mRNA和蛋白的表达呈高度正相关 (rs>0 82 ,Ps<0 0 1)。结论　脑出血后AQP4表达明显增强 ,提示AQP4参与了出血性脑水肿的发生发展过程 ,在出血性脑水肿的形成过程中起重要作用。     

水通道蛋白4在人胶质瘤性脑水肿中的表达

目的 检测人脑胶质瘤及其瘤周组织中的水通道蛋白4(AQP4)的表达,探讨AQP4与胶质瘤性脑水肿发生的相关性.方法 对48例胶质瘤组织、28例胶质瘤瘤周组织和8例对照组进行RT-PCR和Western blot检测胶质瘤组织中AQP4 mRNA和AQP4蛋白的表达.结果 胶质瘤及瘤周组织中AQP4 mRNA表达高于对照组,二组间差异有统计学意义(P＜0.05).结论 AQP4的表达与胶质瘤性脑水肿呈正相关,在胶质瘤性脑水肿的形成过程中起重要作用.     

水通道蛋白4及其在癫痫研究中的进展

自1988年发现第一个水通道蛋白(aquaporin,AQP)l至今.已经在哺乳动物体内发现了至少13种水通道蛋白(AQPs)的存在.这些AQPs是一些四聚体结构的蛋白质分子[1],有6个跨膜区嗣绕舣向流动的水通道.除了 AQP3、AQP7、AQP9,可以允许甘油和极性分子通过外,其余的AQPs仅仅选择性允许水分子通过.AQP4是哺乳动物大脑中主要的AQP,存在于在星形胶质细胞、神经胶质界膜、室管膜等部位,与水分子进出大脑有关.可加速星形胶质细胞迁移和改变神经系统活性.随着研究的深入,它与癫痫的关系越来越受到重视.     

水通道蛋白4在脑出血患者脑内皮层的表达

目的观察水通道蛋白4(aquaporin-4,AQP4)在脑出血继发脑水肿患者脑内皮层的表达。方法采用逆转录聚合酶链式反应(RT-PCR),免疫组织化学和Western-blot技术,分析比较10例脑出血患者脑组织与6例正常脑组织标本AQP4的mRNA和蛋白的表达情况。结果AQP4主要表达在皮层上的星形胶质细胞。脑出血继发脑水肿患者脑组织AQP4的mRNA和蛋白的表达均显著高于正常对照组(P<0.01)。结论AQP4参与了脑出血继发脑水肿的发生,可能是脑水肿产生的重要分子基础。     

水通道蛋白和脑积水

脑积水是脑脊液循环障碍的一种常见表现,水通道蛋白的发现有助于进一步了解脑积水后脑脊液循环的改变和调节。本文就脑内水通道蛋白的表达、调节及其在脑积水治疗中的潜在作用作一综述。     

水通道蛋白4在颅脑损伤组织的表达及临床意义

目的检测颅脑损伤脑水肿组织中AQP4的表达,探讨水通道在颅脑损伤性脑水肿中的表达规律,阐述脑水肿的发生、发展机制。方法对8例颅脑损伤的脑水肿组织和8例对照组织进行逆转录-聚合酶链式反应(RT-PCR)和免疫印迹(Western-Blot),检测颅脑损伤水肿组织中AQP4 mRNA的表达和AQP4蛋白的表达情况。结果RT-PCR经半定量分析和Western-Blot结果显示:颅脑损伤组AQP4表达比正常组明显升高,两组之间有统计学意义。结论颅脑损伤组织中,损伤周围的脑水肿组织AQP4 mRNA和蛋白质的表达与颅脑损伤组织中脑水肿的严重程度呈高度正相关,证明了AQP4参与了颅脑损伤组织中脑水肿的发生和发展过程,在脑水肿的形成过程中起重要作用。     

Caspase 8 expression and signaling in Fas injury-resistant human fetal astrocytes

Fas (APO-1/CD95) is a cell surface receptor initially identified in lymphoid cells, but more recently detected in the central nervous system under pathological, usually inflammatory, conditions. In most Fas expressing cells, triggering of Fas by its ligand or by antagonistic antibodies leads to apoptosis. Human fetal astrocytes (HFA) constitutively express Fas yet are resistant to cell death following Fas ligation. In the current study, using dissociated cultures of human fetal central nervous system-derived cells, we attempted to identify a basis for HFA resistance to Fas-mediated injury. We compared the components of the Fas signaling pathway of HFA to those of two human cell lines susceptible to Fas-mediated injury, U251 glioma and Jurkat T-cells. We found that HFA did not express caspase 8 (FLICE), the caspase primarily activated on Fas signaling. Although we could induce caspase 8 in HFA with the inflammatory cytokines IFNgamma and TNFalpha, HFA remained resistant to Fas-mediated injury. Addition of inflammatory cytokines to the extracellular milieu also increased FLIP mRNA (FLICE inhibitory protein). Furthermore, upon triggering of cytokine-treated cells with FasL, we observed upregulation of the cleavage product of FLIP (p43-FLIP) previously shown to associate with the DISC and to block caspase 8 recruitment, thereby inhibiting Fas-mediated death. Our findings indicate that caspase 8 and its regulators play a central role in determining the response to Fas ligation of HFA and support a role for Fas signaling in the developing central nervous system other than related to cytotoxicity.     

Aquaporin 4 expression in human skeletal muscle fiber types

Introduction: Aquaporins (AQPs) are a family of transmembrane proteins involved in the maintenance of osmotic gradients. AQP4 is abundant in skeletal muscle, where it seems to be associated with glycolytic metabolism. We investigated the pattern of expression of AQP4 in normal human myofibers relative to the main forms of myosin heavy chain (MHC). Methods: Six normal human muscle biopsies were analyzed by double immunofluorescence for co‐expression of AQP4 and slow or fast MHC. Results: A high percentage (64–99%) of MHC‐fast positive fibers showed immunoreaction for AQP4. Immunoreactivity for AQP4 was also present in MHC‐slow positive fibers, but with a higher variability (5–72%) among biopsies. Discussion: The expression pattern of AQP4 in human myofibers is highly variable among different patients and cannot be predicted for single fibers depending on MHC type expression. Other factors, possibly related to muscle activity, may modulate AQP4 expression. Muscle Nerve 57 : 856–859, 2018     

Utrophin expression during human fetal development

Utrophin, a protein encoded by chromosome 6 is highly homologous to the cysteine-rich domain and most of the C-terminal domain of dystrophin. In order to clarify its functional role we analyzed its expression during human fetal development. We carried out immunohistochemical analysis on muscle from normal human fetuses at different ages of gestation using an antibody directed against a specific COOH-terminal sequence of the protein. In addition, we stained serial sections with antibodies against dystrophin and alpha-bungarotoxin FITC-BTX. Our findings show that, at week 9 of gestation, utrophin is diffusely expressed in the cytoplasm. From week 12 to 22 the immunostaining is still cytoplasmic, though the reaction intensity progressively decreases. Moreover we observed a strong reaction in fetal nerve at week 18 and 22. There was no correlation between utrophin expression and progressive dystrophin membrane localization.     

Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain

Prenatal exposure to infection appears to increase the risk of schizophrenia and other neurodevelopmental disorders. We have hypothesized that cytokines, generated in response to maternal infection, play a key mechanistic role in this association. E16 timed pregnancy rats were injected i.p. with Escherichia coli lipopolysaccharide (LPS) to model prenatal exposure to infection. Placenta, amniotic fluid and fetal brains were collected 2 and 8h after LPS exposure. There was a significant treatment effect of low-dose (0.5mg/kg) LPS on placenta cytokine levels, with significant increases of interleukin (IL)-1beta (P<0.0001), IL-6 (P<0.0001), and tumor necrosis factor-alpha (TNF-alpha) (P=0.0001) over the 2 and 8h time course. In amniotic fluid, there was a significant effect of treatment on IL-6 levels (P=0.0006). Two hours after maternal administration of high-dose (2.5mg/kg) LPS, there were significant elevations of placenta IL-6 (P<0.0001), TNF-alpha (P<0.0001), a significant increase of TNF-alpha in amniotic fluid (P=0.008), and a small but significant decrease in TNF-alpha (P=0.035) in fetal brain. Maternal exposure to infection alters pro-inflammatory cytokine levels in the fetal environment, which may have a significant impact on the developing brain.     

MMP-8在颈动脉粥样斑块中的表达

目的 研究基质金属蛋白酶 8(MMP 8)在颈动脉不同类型粥样斑块中的表达与斑块破裂的关系。 方法30例人体成熟型颈动脉粥样斑块来源于颈动脉内膜剥脱术取材 ,由组织病理学分为稳定型 (16例 )和不稳定型(14例 )两组 ,6例来源于肝移植供者正常腹主动脉和分支为对照组。用免疫组化的方法测定MMP 8在粥样斑块不同细胞成分中的表达。结果 在稳定型斑块中 ,MMP 8表达 9例 ,不稳定型斑块中MMP 8表达 13例 ,对照组无表达 (P <0 .0 5 ) ,且在不稳定型斑块中MMP 8表达量明显上调 ,每个高倍视野阳性细胞计数不稳定型斑块为79 .5 7± 6 .74 ,稳定型斑块为 34.4 4± 7.2 5 (P =0 .0 0 0 1)。MMP 8表达不仅存在于单核—巨噬细胞 ,而且也存在于平滑肌细胞和泡沫细胞。结论 MMP 8在颈动脉不稳定型斑块中的表达明显高于稳定型斑块 ,可能是决定斑块不稳定性的重要相关因子之一。数据有可能为筛选抑制剂和基因治疗颈动脉狭窄提供参考。     

Musashi1 antigen expression in human fetal germinal matrix development

Musashi1 is a highly conserved protein found in neural progenitor cells. We examined the expression dynamics of Musashi1 in conjunction with other representative neural progenitor antigenic determinants (Ki-67 and nestin) during 8 different stages of the developing human fetal germinal matrix. Our results indicate that Musashi1 is a useful marker for immature cells in periventricular areas inhabited by stem cells, progenitor cells, and differentiating cells.     

Functional expression of CCR2 by human fetal astrocytes

Astrocytes from different sources bind the chemokine monocyte chemoattractant factor (MCP-1), yet functional expression in these cells of CCR2, the major receptor for this ligand, has been a matter of controversy. Here we show that cultured human fetal astrocytes express CCR2 at the mRNA and protein levels, and display chemotaxis and calcium flux in response to MCP-1. Surface CCR2 protein expression and MCP-1 binding activity were observed to undergo near parallel downmodulation and recovery following MCP-1 exposure, supporting the argument that CCR2, and not another receptor, mediates MCP-1 ligation in these cells. Downmodulation was further determined to occur via receptor internalization, and to apparently proceed via both clathrin-coated vesicles and caveolae, the latter being a novel mode for the endocytosis of chemokine receptors. Insofar as MCP-1 is thought to mediate inflammatory and developmental processes within the central nervous system (CNS), such astrocyte responses to this chemokine are likely to significantly impact physiological and pathophysiological events at the blood-brain barrier and within the CNS parenchyma.