亚低温对脑心综合征大鼠血清皮质酮变化的影响及意义

目的探讨亚低温对急性脑梗死(ACI)并发脑心综合征(CCS)大鼠血清皮质酮(CORT)变化的影响及意义。方法将实验大鼠随机分为亚低温组、常温组及假手术组,亚低温组及常温组采用线栓法栓塞大鼠右侧大脑中动脉,术后连续监测标准Ⅱ导联心电图2h,统计各组脑心综合征的发病率,检测术后2h、24h、48h血清皮质酮的水平。结果亚低温组较常温组脑心综合征发病率低(P0.05);常温组及亚低温组各时间点皮质酮水平均较假手术组增高,差异有统计学意义(P0.05),常温组各时间点皮质酮水平均较亚低温组高,但只在2h点差别有统计学意义(P0.05)。结论亚低温可能通过稳定应激激素的水平降低急性脑梗死大鼠并发脑心综合征的发病率。     

脑型脂肪酸结合蛋白在急性脑梗死检测方面的临床意义

目的探讨脑型脂肪酸结合蛋白（B-FABP）在急性脑梗死（ACI）发病过程中的动态变化及临床意义。方法采用ELISA检测100例ACI患者发病l d内、第7d和第l4d内的血清B-FABP,分析其与梗死部位、大小及神经功能缺损的关系。结果 100例脑梗死患者发病l d内、第7d和第l4d血清B-FABP含量水平均明显高于对照组（P〈0.01）,其中在急性期（发病1d内）B-FABP敏感性达68%;腔隙性梗死组B-FABP水平明显高于其它三组（P〈0.01）,全前循环梗死组的B-FABP水平高于后循环梗死组与部分前循环梗死组（P〈0.05）,后循环梗死组高于部分前循环梗死组（P〈0.05）;B-FABP水平在小病灶梗死组高于大病灶梗死组、中病灶组（P〈0.01）,而大病灶梗死组高于中病灶组（P〈0.05）;B-FABP水平在轻型组高于重型组、中型组（P〈0.01）;重型组高于中型组（P〈0.05）。结论 ACI患者血清中B-FABP水平变化与梗死部位、大小和病情严重程度有关,其高敏感性可作为早期诊断脑梗死的潜在、快速的生物学指标。     

急性脑梗死患者神经功能缺损程度与血清H-FABP、CD62P水平的关系

目的 探讨急性脑梗死患者神经功能缺损程度与血清心型脂肪酸结合蛋白(H-FABP)、血小板α颗粒膜蛋白(CD62P)的关系。方法 选择本院收治的180例急性脑梗死患者为研究对象,将其分为轻度组、中度组、重度组3组,每组各60例,以同期体检健康者60例为对照组; 采用神经功能缺损评分量表(NIHSS评分)评定急性脑梗死患者神经功能缺损程度,通过酶联免疫吸附法(ELISA)检测各组血清神经功能缺损指标(NES、S100B)及H-FABP、CD26P水平,分析神经功能缺损程度与血清H-FABP、CD26P的关系。结果 急性脑梗死重度组与中度组NIHSS评分、NES及S100B水平均高于急性脑梗死轻度组,而中度组高于轻度组(P<0.01); 急性脑梗死组血清H-FABP、CD26P水平均高于对照组,急性脑梗死重度组与中度组高于急性脑梗死轻度组,而中度组血清H-FABP、CD26P水平高于轻度组(P<0.01); 急性脑梗死患者血清H-FABP、CD26P水平与神经功能缺损程度呈正相关。结论 急性脑梗死患者神经功能缺损程度与血清H-FABP、CD26P水平呈显著正相关,推测临床可参照血清H-FABP、CD26P水平来评估急性脑梗死患者神经功能缺损程度。     

心型脂肪酸结合蛋白在神经系统疾病中的研究

脂肪酸结合蛋白(fatty acid-binding proteins,FABP)家族是由一组多源性的细胞内小分子蛋白质组成,广泛分布于哺乳动物及人类的心、肝、小肠、脂肪、脑、骨骼肌等细胞.近年的研究表明心型脂肪酸结合蛋白(heart-fatty acid binding protein,H-FABP)可以作为心肌梗死诊断、预后的敏感、有效生化标志物,亦有研究提示H-FABP可以作为脑梗死诊断、预后等判断的生化标志物.近年来对于H-FABP的研究更进一步揭示H-FABP可能与痴呆、代谢综合征等疾病相关.本文就H-FABP 的在中枢神经系统疾病中的研究状况进行复习.     

MBPH-FABP MCP-1与脑梗死病情分期及预后的相关性分析

目的分析髓鞘碱性蛋白(MBP)、心型脂肪酸结合蛋白(H-FABP)、单核细胞趋化蛋白1(MCP-1)与脑梗死病情、分期关联性及预后的关系。方法选取2017-05—2019-05郑州大学第一附属医院治疗的脑梗死患者106例为研究组,另选取同期健康体检者106例为对照组。入院后抽取受检者空腹肘正中静脉血样本,经酶联免疫吸附法(ELISA)测定血清MBP、H-FABP、MCP-1水平。检测研究组与对照组、研究组不同病情及不同分期、不同预后患者血清MBP、H-FABP、MCP-1水平,分析血清指标与脑梗死病情、分期、预后的相关性,应用Logistic回归分析脑梗死发病的危险因素。结果研究组血清MBP、H-FABP、MCP-1水平高于对照组(P0.05);经Logistic回归分析,MBP(OR=2.760)、H-FABP(OR=2.619)、MCP-1(OR=2.210)是脑梗死发病的独立危险因素(P0.05);研究组中度患者血清MBP、H-FABP、MCP-1水平高于轻度患者,重度患者血清MBP、H-FABP、MCP-1水平高于中度患者(P0.05);急性期患者血清MBP、H-FABP、MCP-1水平高于恢复期(P0.05);发病后1个月,预后不良患者血清MBP、H-FABP、MCP-1水平高于预后良好患者(P0.05);经Pearson相关性分析,血清MBP(r_1=0.776,r_2=0.761,r_3=-0.801)、H-FABP(r_1=0.811,r_2=0.798,r_3=-0.789)、MCP-1(r_1=0.823,r_2=0.759,r_3=-0.783)水平与病情、分期呈正相关,与预后呈负相关(P0.05)。结论血清MBP、H-FABP、MCP-1水平在脑梗死患者中呈高表达状态,均属于脑梗死发病的独立危险因素,且与病情、分期、预后密切相关,可作为预测脑梗死预后的重要因子。     

血清NSE、Hcy及H-FABP检测在急性脑梗死诊断中的应用价值

目的探讨血清神经元特异性烯醇化酶(NSE)、同型半胱氨酸(Hcy)及心型脂肪酸结合蛋白(H-FABP)检测在急性脑梗死(ACI)诊断中的应用价值。方法分析100例ACI患者(观察组)和100例健康体检者(对照组)血清NSE、Hcy及H-FABP水平差异,对比不同病灶直径及神经损伤程度ACI患者血清NSE、Hcy及H-FABP水平;分析各指标对ACI的诊断价值。结果观察组血清NSE、Hcy及H-FABP水平均显著高于对照组(P0.05)。随病灶直径的增加和神经损伤程度的加重,血清NSE、Hcy及H-FABP水平也显著升高(P0.05)。ACI患者血清NSE、Hcy及H-FABP水平与病灶直径及患者NIHSS评分均呈显著正相关(P0.05)。血清NSE、Hcy及H-FABP诊断ACI的ROC曲线下面积分别为0.913、0.872、0.822,其诊断敏感度为72.0%、73.0%、77.0%,特异度为97.0%、88.0%、71.0%。结论血清NSE、Hcy及H-FABP水平随ACI患者病灶直径及神经损伤程度的加重而升高,三者可作为ACI临床诊断和评估病情的重要实验室指标。     

伴B-FABP增高的缺血性卒中相关危险因素分析

目的探讨伴脑型脂肪酸结合蛋白(B-FABP)增高的缺血性卒中患者的相关危险因素。方法以2015-09—2016-09我院收治的54例伴B-FABP增高的缺血性脑卒中患者为研究组,以同期收治的非B-FABP增高的缺血性脑卒中患者54例为对照组。对比2组一般资料,并对研究组患者的相关危险因素进行分析。结果性别(男)、冠心病、高血压、饮酒、吸烟、糖尿病、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白等为伴B-FABP增高的缺血性脑卒中患者的相关危险因素(P0.05),且性别(男)、冠心病、高血压、饮酒、吸烟、糖尿病、甘油三酯、总胆固醇、低密度脂蛋白与缺血性脑卒中患者B-FABP增高呈正相关(P0.05),而高密度脂蛋白与B-FABP增高呈负相关(P0.05);Logistic多因素回归分析显示,缺血性脑卒中患者B-FABP增高的独立危险因素为高血压及糖尿病,保护因素为高密度脂蛋白。结论影响缺血性脑卒中患者B-FABP水平的主要危险因素为高血压、糖尿病、高密度脂蛋白。临床需采取积极措施,加强对高危人群相关危险因素的监测,并尽早采取积极措施进行干预,从而最大限度减少缺血性脑卒中。     

参附注射液治疗急性脑梗死后脑心综合征临床观察

目的分析参附注射液对急性脑梗死后脑心综合征的治疗效果。方法脑心综合征患者92例,随机分为治疗组与对照组各46例,治疗组在常规治疗基础上给予参附注射液治疗,对照组给予常规治疗。对比2组临床症状、心电图及血清心肌酶变化情况。结果治疗组总有效率为91.3%,显著高于对照组的71.7%(P0.01);治疗后治疗组心律失常、ST-T改变、心肌酶改变与对照组比较差异有统计学意义(P0.05)。结论参附注射液对于急性脑梗死后脑心综合征的疗效确切。     

脑红蛋白在脑梗死大鼠表达及丁苯酞干预效应

目的探讨脑红蛋白在脑梗死大鼠中的表达和丁苯酞干预在氧化应激损伤中作用。方法将90只雄性SD大鼠随机分为假手术组、模型组、治疗组。每组再分为3个亚组:1 d组、3 d组和7 d组,每亚组10只。模型组和治疗组采用线栓法制作大鼠大脑中动脉闭塞模型(MCAO),假手术组只分离不结扎。治疗组在动物苏醒后以丁苯酞植物油灌胃,假手术组和模型组同法给予等量植物油灌胃。每只大鼠在术后3h和处死前行神经功能评分,应用RT-PCR和免疫组化检测脑组织脑红蛋白(NGB)表达,化学比色法检测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果 (1)神经功能评分,模型组和治疗组术后3 h评分差异无统计学意义(P>0.05),各时间点处死前评分差异均有统计学意义(P<0.05)。(2)NGB mRNA和免疫组化表达随时间延长逐渐降低,各时间点模型组较假手术组、治疗组较模型组高,差异均有统计学意义(P<0.05)。(3)SOD活性和MDA含量随时间延长逐渐减少。SOD活性假手术组较治疗组、治疗组较模型组高,差异均有统计学意义(P<0.05);MDA含量假手术组较治疗组、治疗组较模型组低,差异均有统计学意义(P<0.05)。结论丁苯酞促进脑缺血大鼠脑红蛋白表达,减少氧化应激损伤。     

脑源性神经营养因子融合蛋白对大鼠局灶性脑缺血治疗作用的初步研究

目的 研究脑源性神经营养因子融合蛋白(BDNF-PTD)在大鼠脑缺血模型中对大脑神经元的保护作用.方法 SD大鼠采用随机数字表法分为给药模型组、空白模型组、阴性对照组、正常组,每组5只.前3组大鼠通过线栓法制作脑中动脉栓塞模型;正常组大鼠正常喂养.不做任何处理.栓塞1 h后给药模型组腹腔注射50 μg(50 μg/mL)BDNF-PTD,阴性对照组注射1 mL生理盐水,空白模型组不做处理.采用Bederson评分评价各组大鼠神经功能缺损情况.24h后将各组大鼠断头取脑,大脑切片TTC染色,观察各组大鼠脑梗死面积.结果 给药模型组大鼠神经功能缺损不明显,Bederson评分明显低于空白模型组及阴性对照组(P<0.05).TTC染色结果提示给药模型组大鼠脑梗死区域面积较空白模型组、阴性对照组明显缩小,差异有统计学意义(P<0.05).结论 BDNF-PTD能通过血脑屏障并且发挥其生物学效应.起到保护脑缺血后神经元作用.     

Involvement of membrane-associated proteins in the acute regulation of cellular fatty acid uptake

The transport of long-chain fatty acids across cellular membranes most likely occurs to some extent by passive diffusion and additionally is facilitated by a number of membrane-associated and cytoplasmic proteins. In this overview we focus on the involvement of the membrane proteins fatty acid translocase (FAT/CD36), plasma membrane fatty acid-binding protein (FABP_pm) and fatty acid-transport protein (FATP). Newly obtained evidence is presented that in skeletal muscle, fatty acid uptake is subject to short-term regulation by translocation of FAT/CD36 from intracellular stores to the plasma membrane, analogous to the regulation of muscular glucose uptake by GLUT-4 translocation. These new findings establish a significant role of membrane-associated proteins in the cellular fatty acid-uptake process. Possible implications for the uptake and transport of long-chain fatty acids by the brain are discussed.     

Fatty acid binding protein 4 is expressed in distinct endothelial and non-endothelial cell populations in glioblastoma

O. Cataltepe, M. C. Arikan, E. Ghelfi, C. Karaaslan, Y. Ozsurekci, K. Dresser, Y. Li, T. W. Smith and S. Cataltepe (2012) Neuropathology and Applied Neurobiology 38, 400–410 Fatty acid binding protein 4 is expressed in distinct endothelial and non‐endothelial cell populations in glioblastoma Aims: Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults. Angiogenesis and vasculogenesis play key roles in progression of GBMs. Fatty acid binding protein 4 (FABP4) is an intracellular chaperone for free fatty acids. FABP4 is detected in microvascular endothelial cells (ECs) in several normal tissues and promotes proliferation of ECs. The goal of this study was to characterize the tissue distribution pattern of FABP4 in GBMs. Methods: Immunohistochemistry for FABP4 was performed on paraffin‐embedded tumour sections and the intensity and distribution of FABP4 immunoreactivity were analysed. Double immunofluorescence was employed for detailed characterization of FABP4‐positive cells. Results: FABP4 immunoreactivity was absent in normal brain tissue sections. FABP4‐positive cells were detected in 33%, 43%, 64% and 89% of Grade I, Grade II, Grade III and Grade IV glial tumours, respectively. Thus, the percentage of FABP4‐positive cells in GBMs was significantly higher than lower‐grade gliomas. In general, FABP4‐expressing cells were distributed in a non‐homogenous pattern, as ‘hot spots’ in glial tumours. FABP4 expression was detected in a subset of vascular ECs as well as some non‐ECs. Conclusion: FABP4 is expressed in a significantly higher percentage of GBMs in comparison to both normal brain tissues and lower‐grade glial tumours. FABP4 is expressed in some tumour ECs as well as non‐ECs in glial tumours. As FABP4 promotes proliferation of ECs, detection of FABP4 in GBM‐ECs, but not normal brain ECs suggests that FABP4 may play a role in the robust angiogenesis associated with GBMs.     

Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury

Peripheral nerve trauma induces the expression of genes presumed to be involved in the process of nerve degeneration and repair. In the present study, an in vivo paradigm was employed to identify molecules which may have important roles in these processes. A cDNA library was constructed with RNA extracted from rat dorsal root ganglia (DRG) 3 days after a sciatic nerve crush. After differential hybridization to this library, several cDNAs were identified that encoded mRNAs that were upregulated in the DRG ipsilateral to the crush injury, as opposed to the contralateral or naive DRG. Approximately 0.15% of all the clones screened were found to be induced. This report presents the types of induced sequences identified and characterizes one of them, DA11. The 0.7 kb DA11 full length cDNA clone contains a 405 nucleotide open reading frame that encodes a putative protein of 15.2 kDa (135 amino acid residues) and is a member of the family of fatty acid binding proteins (FABP). The DA11 protein differs by one amino acid residue from the sequence of the C-FAPB protein and by eight residues from the sequence of mal1, proteins found in rat and mouse skin, respectively. Northern and Western blot analyses showed that the DA11 mRNA and protein were induced in the injured DRG. Furthermore, studies using antibodies generated against DA11 found that the DA11-like immunoreactivity was more pronounced in the nuclei of neurons located in the DRG ipsilateral to the sciatic cut than those located in the contralateral DRG. The induction of DA11 mRNA and protein in DRG neurons suggests, for the first time, the involvement of a neuronal FABP in the process of degeneration and repair in the nervous system. © 1996 Wiley-Liss, Inc.     

The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination

The major constituents of the myelin sheath are lipids, which are made up of fatty acids (FAs). The hydrophilic environment inside the cells requires FAs to be bound to proteins, preventing their aggregation. Fatty acid binding proteins (FABPs) are one class of proteins known to bind FAs in a cell. Given the crucial role of FAs for myelin sheath formation we investigated the role of FABP7, the major isoform expressed in oligodendrocyte progenitor cells (OPCs), in developmental myelination and remyelination. Here, we show that the knockdown of Fabp7 resulted in a reduction of OPC differentiation in vitro. Consistent with this result, a delay in developmental myelination was observed in Fabp7 knockout animals. This delay was transient with full myelination being established before adulthood. FABP7 was dispensable for remyelination, as the knockout of Fapb7 did not alter remyelination efficiency in a focal demyelination model. In summary, while FABP7 is important in OPC differentiation in vitro, its function is not crucial for myelination and remyelination in vivo.     

Origin,maturation, and astroglial transformation of secondary radial glial cells in the developing dentate gyrus

The dentate gyrus is a brain region where neurons are continuously born throughout life. In the adult, the role of its radial glia in neurogenesis has attracted much attention over the past years; however, little is known about the generation and differentiation of glial cells and their relationship to radial glia during the ontogenetic development of this brain structure. Here, we combine immunohistochemical phenotyping using antibodies against glial marker proteins with BrdU birthdating to characterize the development of the secondary radial glial scaffold in the dentate gyrus and its potential to differentiate into astrocytes. We demonstrate that the expression of brain lipid‐binding protein, GLAST, and glial fibrillary acidic protein (GFAP) characterizes immature differentiating cells confined to an astrocytic fate in the early postnatal dentate gyrus. On the basis of our studies, we propose a model where immature astrocytes migrate radially through the granule cell layer to adopt their final positions in the molecular layer of the dentate gyrus. Time‐lapse imaging of acute hippocampal slices from hGFAP‐eGFP transgenic mice provides direct evidence for such a migration mode of differentiating astroglial cells in the developing dentate gyrus. © 2010 Wiley‐Liss, Inc.     

Brain‐specific fatty acid‐binding protein is elevated in serum of patients with dementia‐related diseases

Background: There is a need for biomarkers in accessible matrices, such as blood, for the diagnosis of neurodegenerative diseases. The aim of this study was to measure the serum levels of brain‐type fatty acid‐binding protein (FABP) and heart‐type FABP in patients with dementia‐involving diseases. Methods: Brain‐ and heart‐type FABP were measured in serum samples from patients with either Alzheimer’s disease (AD) (n = 31), Parkinson’s disease (PD, n = 43), or other cognitive disorders (OCD, n = 42) and in 52 healthy controls. The localization of brain‐ and heart‐type FABP was determined in brain sections by immunohistochemistry. Results: Brain‐type FABP levels were elevated in serum of 29%, 35%, and 24% of the patients with AD, PD, and OCD, respectively, and in 2% of the healthy donors. Heart‐type FABP serum levels were not different amongst the patient groups. Brain‐type and heart‐type FABP expression was observed in reactive astrocytes in brain sections of patients with AD. Conclusions: In contrast to heart‐type FABP, serum levels of brain‐type FABP are elevated in a significant proportion of patients with various neurodegenerative diseases and can therefore have importance for defining subgroups of these patients.     

Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case

Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X‐linked adrenoleukodystrophy (X‐ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B‐cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS‐like pathology.     

Collision-mediated transfer of long-chain fatty acids by neural tissue fatty acid-binding proteins (FABP)

Mammalian fatty acid-binding proteins (FABP) are a family of intracellular proteins (approx 15 kDa) that bind long-chain fatty acids (FA) with high affinity. They are believed to serve as cytoplasmic transporters of FA and to target FA to specific cellular sites of utilization. Several different FABPs are expressed in neural tissue, including brain FABP (B-FABP), myelin FABP (M-FABP), and heart FABP (H-FABP). We have previously shown that H-FABP transfers FA via direct collisional interactions with acceptor model membranes. In the present studies, we use a fluorescence resonance energy transfer (FRET) assay to examine the rate and mechanism of transfer of a fluorescent long-chain fatty acid from B-FABP to phospholipid vesicles. The rate of transfer is shown to be independent of buffer ionic strength and dramatically enhanced by the presence of specific anionic phospholipids. These results are consistent with a mechanism by which FA are transferred from B-FABP to phospholipid membranes by a transient collision-based mechanism.