改构型酸性成纤维细胞生长因子对细胞增殖活性的影响

目的:研究aFGF和MaFGF对正常的肾小管上皮细胞及胃癌细胞增殖的影响。方法:用不同浓度的aFGF和MaFGF分别作用于肾小管上皮细胞及胃癌细胞,48h后采用WST-8法测定aFGF和MaFGF对两种细胞的促增殖活性。结果:在各浓度下,MaFGF组对肾小管上皮细胞和胃癌细胞的促增殖作用都显著低于aFGF组。结论:MaFGF对肾小管上皮细胞及胃癌细胞的促分裂活性较aFGF明显下降。     

血清血管内皮细胞生长因子和碱性成纤维细胞生长因子水平变化对服药自杀青少年心理状况的影响

摘要 目的：研究服药自杀青少年血清血管内皮细胞生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）变化,及其与患者心理状况的相关性。方法：纳入2018年1月到2020年12月四川大学华西医院收治的服药自杀青少年81例（研究组）,同时纳入81例健康志愿者作为对照（对照组）。检测两组研究对象血清VEGF和bFGF水平,并使用汉密顿抑郁量表（HAMD）、抑郁自评量表（SDS）和自杀意念自评量表（SlOSS）评估两组患者心理状态。结果：两组研究对象性别、年龄、身高以及体质指数（BMI）具有可比性（P>0.05）;研究组吸烟者比例（16/81）和有家族精神病史比例（13/81）均显著高于对照组（6/81和3/81）（P<0.05）。研究组服药自杀青少年血清VEGF（699.72±103.42）ng/mL和bFGF（348.31±65.13）ng/mL水平均高于与对照组健康志愿者[（620.31±85.32）ng/mL和（265.37±35.23）ng/mL]（P<0.05）,并且与是否吸烟或有无家族精神疾病史无关（P<0.05）。Pearson相关性分析结果显示：服药自杀青少年血清VEGF和BFGF均与HAMD和SDS评分无相关,与SIOSS评分均呈正相关（r=0.278和r=0.302,均P<0.05）。结论：服药自杀青少年血清VEGF和bFGF水平升高,与自杀意念自评量表得分有正相关。     

妊娠期糖尿病患者血清NRG4、FGF-23、PGRN水平及其临床意义

摘要 目的：探讨妊娠期糖尿病患者血清神经调节蛋白4(NRG4)、成纤维细胞生长因子-23(FGF-23)、前颗粒体蛋白(PGRN)水平及其临床意义。方法：选择2018年4月至2019年11月我院诊治的90例妊娠期糖尿病患者作为糖尿病组,选择同期在我院进行健康体检的90名健康孕妇作为对照组。检测两组血清NRG4、FGF-23、PGRN水平,血脂指标[高密度脂蛋白（HDL）、总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）]水平,肝功能指标[谷草转氨酶（AST）、谷丙转氨酶(ALT)]水平,血糖和胰岛素指标[空腹血糖（FPG）、空腹胰岛素(FINS)]水平,并计算抗胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数（ISI）和胰岛?茁细胞功能指数(HOMA-β)。分析各临床指标间的关系。结果：与对照组相比,糖尿病组体质量指数（BMI）、TG、TC、FPG、FINS、HOMA-IR、NRG4、FGF-23、PGRN明显升高（P<0.05）,ISI和HOMA-β明显下降（P<0.05）。血清NRG4、FGF-23、PGRN与ISI和HOMA-β均呈负相关（P<0.05）,与BMI、TG、TC、FPG、FINS、HOMA-IR均呈正相关（P<0.05）。TG与NRG4表达联系密切（β=0.007,P<0.05）,ISI和HOMA-IR与FGF-23表达联系密切（β=-6.674、0.048,P<0.05）,FPG和TC与PGRN表达联系密切（β=22.308、0.507,P<0.05）。结论：妊娠期糖尿病患者血清NRG4、FGF-23、PGRN水平异常升高,并参与妊娠期糖尿病患者的糖脂代谢和胰岛素抵抗,检测其水平有助于评估妊娠期糖尿病的糖脂代谢异常情况。     

酸性成纤维细胞生长因子研究进展

酸性成纤维细胞生长因子(acidic fibroblast growth factors,aFGF)是成纤维细胞生长因子家族(fibroblast growth factors,FGF)中的一员,是一种重要的生长因子,具有广泛的生物活性和临床应用价值.本文概述了aFGF的结构与功能关系和信号传导通路,阐述了aFGF生理功能与生物学效应以及潜在临床应用价值.     

碱性成纤维细胞生长因子对培养的瘢痕成纤维细胞FN合成的调控作用

目的探讨碱性成纤维细胞生长因子（bFGF）对成纤维细胞纤维连结蛋白（FN）合成的调控作用。方法采用细胞培养、ELISA法、RT-PCR方法观察bFGF在不同剂量下对瘢痕来源的成纤维细胞FN合成的影响。结果FN的表达在低bFGF浓度组与对照组无明显差异,随着浓度的升高表现为增高趋势,以50、100、500ng／ml最显著,与对照组之间有显著性差异（P〈0．05）。FN mRNA表达在50-100ng／ml组明显升高,与对照组间有显著性差异（P〈0．05）。mRNA表达趋势与上清中蛋白的表达具有一致性。结论高浓度bFGF刺激FN合成可能是bFGF促进创面愈合的重要原因。     

改构酸性成纤维细胞生长因子对小鼠胸腺细胞凋亡的影响

目的:探讨改构酸性成纤维细胞生长因子(MaFGF)对地塞米松(DEX)诱导小鼠胸腺细胞凋亡的保护作用。方法:利用地塞米松诱导小鼠胸腺细胞凋亡的模型,将实验分为空白对照组、DEX处理组、aFGF+DEX组和MaFGF+DEX组,采用DNA琼脂糖凝胶电泳和流式细胞仪两种分析方法,测定MaFGF对小鼠胸腺细胞凋亡的影响。结果:空白对照组凋亡率为168%,DEX处理后小鼠胸腺细胞出现明显的细胞凋亡,凋亡率为196%,aFGF和MaFGF处理后的细胞凋亡受到抑制,凋亡率分别下降到1595%和1293%,MaFGF效应强于aFGF,且以剂量依赖方式发挥作用。结论:MaFGF具有以剂量依赖方式的胸腺细胞保护作用。     

碱性成纤维细胞生长因子对激光烧伤大兔皮肤愈合的影响分析

摘要 目的：探讨碱性成纤维细胞生长因子对激光烧伤大兔皮肤愈合的影响分析。方法：通过热辐射仪激光灼烧对大兔耳朵进行烧伤处理,根据实验需求,将其随机分为三组：对照组,bFGF组,bFGF + DAPT组。通过ImageJ软件测量伤口面积和疤痕组织的厚度,并定期计算残余伤口面积率和疤痕指数。通过组织学分析大兔伤口愈合的新血管生成量。通过蛋白印迹分析Notch1、Jagged1和Hes1的蛋白表达。通过免疫荧光分析愈合后的皮肤中α-SMA,Col I和Col III的相对蛋白水平。结果：bFGF组较对照组的疤痕指数降低（P<0.05）,bFGF+DAPT组较bFGF组疤痕指数升高（P<0.05）。bFGF组较对照组的愈合面积增加（P<0.05）,bFGF + DAPT组较bFGF组愈合面积降低（P<0.05）。与对照组相比,bFGF组的愈合时间明显缩短,较低的残余伤口面积和较低的疤痕指数（P<0.05）,而bFGF + DAPT组表现出明显的愈合延迟和较高的疤痕指数（P<0.05）。bFGF组较对照组的新血管生成量增加（P<0.05）,bFGF + DAPT组较bFGF组心血管生成量减少（P<0.05）。bFGF组较对照组的肉芽组织平均厚度增加,表皮间隙的闭合百分比升高（P<0.05）,bFGF + DAPT组较bFGF组肉芽组织平均厚度增加、表皮间隙的闭合百分比减少（P<0.05）。H＆E染色进行组织学分析发现,与对照组和bFGF + DAPT组相比,bFGF组出现明显的再上皮化和新血管形成,愈合效率较高（P<0.05）。bFGF组较对照组Notch1、Jagged1和Hes1的蛋白表达升高（P<0.05）,bFGF + DAPT组较bFGF组Notch1、Jagged1和Hes1的蛋白表达降低（P<0.05）。bFGF组较对照组?琢-SMA,Col I和Col III的蛋白表达降低（P<0.05）,bFGF + DAPT组较bFGF组表达升高（P<0.05）。结论：bFGF可以通过促进ESC的增殖并通过激活Notch1 / Jagged1途径抑制其向肌成纤维细胞（Myofibroblasts,MFB）的分化加快伤口愈合,减少疤痕形成。     

人酸性成纤维细胞生长因子神经营养作用的初步研究

本实验研究了人酸性成纤维细胞生长因子(haFGF)的体外神经营养作用。结果表明,haFGF在体外能明显促进鸡胚(E-8)脊髓组织神经突起的生长,并能明显改变新生大鼠脑星形胶质细胞的形态,使扁平、多角形紧密联接的细胞转化为具有纤维样突起的胶质细胞,同时对胶质细胞DNA合成也有一定促进作用。实验还证明,haFGF可增加体外培养新生大鼠海马神经元的存活,且大大增加神经元胞体体积及突起长度。     

冠心病患者血清成纤维细胞生长因子23、碱性磷酸酶及胎球蛋白A水平与冠状动脉钙化的关系及其预测价值分析

摘要 目的：分析冠心病（CHD）患者血清成纤维细胞生长因子23（FGF23）、碱性磷酸酶（ALP）、胎球蛋白A（FA）水平与冠状动脉钙化（CAC）的关系并探讨其对CAC的预测价值。方法：选取2021年2月～2022年2月本院收治的165例CHD患者,根据是否伴有CAC分为CAC组（n=73）和非CAC组（n=92）。收集患者临床资料,采用酶联免疫吸附法（ELISA）检测血清FGF23、ALP、FA水平。通过多因素Logistic回归分析CHD患者CAC的影响因素,绘制受试者工作特征（ROC）曲线分析血清FGF23、ALP、FA水平对CHD患者CAC的预测价值。结果：CAC组血清FGF23、ALP水平高于非CAC组,血清FA水平低于非CAC组（均P＜0.01）。多因素Logistic回归分析显示,年龄（较大）（OR=1.220,95％CI：1.087～1.369）、高血压病（OR=1.461,95％CI：1.062～2.010）、血钙（较高）（OR=1.532,95％CI：1.042～2.251）、血磷（较高）（OR=1.209,95％CI：1.097～1.333）、FGF23（较高）（OR=1.012,95％CI：1.007～1.018）、ALP（较高）（OR=1.046,95％CI：1.023～1.070）为CHD患者CAC的独立危险因素,FA（较高）（OR=0.827,95％CI：0.750～0.912）为独立保护因素（均P＜0.05）。ROC曲线分析显示,血清FGF23、ALP、FA单独与联合预测CHD患者CAC的曲线下面积（AUC）分别为0.790、0.773、0.786、0.915,联合预测CHD患者CAC的AUC大于各指标单独预测。结论：血清FGF23、ALP水平升高和FA水平降低与CHD患者发生CAC密切相关,可作为CHD患者发生CAC的辅助预测指标,且三个指标联合预测CHD患者CAC发生风险的价值较高。     

血清骨桥蛋白、胸苷激酶1、成纤维细胞生长因子受体4与局部晚期宫颈癌患者新辅助化疗疗效的关系研究

摘要 目的：探讨血清骨桥蛋白（OPN）、胸苷激酶1（TK1）、成纤维细胞生长因子受体4（FGFR4）与局部晚期宫颈癌（LACC）患者新辅助化疗疗效的关系。方法：选择2011年8月至2019年7月贵州医科大学附属肿瘤医院收治的160例LACC患者,均接受3个周期的紫杉醇和卡铂新辅助化疗,根据疗效将患者分为有效组和无效组。化疗前检测血清OPN、TK1、FGFR4水平,比较两组上述指标差异。收集相关资料,以多因素Logistic回归分析LACC患者新辅助化疗疗效的影响因素。采用受试者工作特征（ROC）曲线分析OPN、TK1、FGFR4对新辅助化疗疗效的预测价值。结果：160例患者均顺利完成新辅助化疗,治疗有效129例（有效组）,无效31例（无效组）。无效组血清OPN、TK1、FGFR4水平均高于有效组（P＜0.05）。多因素Logistic回归分析结果显示,FIGO分期为Ⅲ期、IVA期以及血清OPN、TK1、FGFR4水平较高是影响LACC患者新辅助化疗疗效的危险因素（P＜0.05）。血清OPN、TK1、FGFR4预测LACC患者新辅助化疗疗效的ROC曲线下面积分别为0.831、0.695、0.767,三项联合预测的曲线下面积为0.893,高于各指标单独检测。结论：LACC患者新辅助化疗疗效受到FIGO分期和血清OPN、TK1、FGFR4水平影响,联合检测血清OPN、TK1、FGFR4水平对LACC患者新辅助化疗疗效具有一定的预测价值。     

Mouse Monoclonal Antibodies Reacting with Human Brain Glial Fibrillary Acidic Protein

Abstract: Three different epitopes on the glial fibrillary acidic protein (GFAP) have been identified by means of three monoclonal antibodies. The antibodies were named anti-GFAP 1, anti-GFAP 2, and anti-GFAP 3. Antibody specificities were investigated by several techniques including indirect immunoprecipitation, immunoblotting, and immunohistochemistry. The anti-GFAP 1 antibodies recognized an epitope found on GFAP from all three species tested: human, rat, and ox, but in addition a reaction was observed with cells not containing GFAP. The epitope recognized by anti-GFAP 2 was present on GFAP from human and ox, but apparently not on rat GFAP; the anti-GFAP 2 antibodies also reacted with antigen(s) other than GFAP. In contrast, the epitope defined by anti-GFAP 3 has proved absolutely specific for GFAP in human, rat, and ox.     

Cell Growth Suppression of Astrocytoma C6 Cells by Glial Fibrillary Acidic Protein cDNA Transfection

Abstract: The cellular functions of the intermediate filament family including glial fibrillary acidic protein (GFAP) are not well known yet beyond their roles as structural elements of cells. Expression of GFAP, which is specific in astrocytes and regulated developmentally, suggests its involvement in cell growth and differentiation of astrocytes. We transfected murine GFAP cDNA into a rat astrocytoma C6 cell line to assess the specific effect of GFAP on cells. Two stable GFAP-transfected cell lines, GFC6-5 and GFC6-6, exhibited a series of morphological and growth characteristics that distinguish them from their counterparts, i.e., NeoC6 cells transfected only with the neomycin-resistant gene, and native C6 cells. Both GFC6-5 and GFC6-6 cells showed elongated cell shapes with extended processes rich in GFAP, markedly suppressed cell growth, and decreased bromodeoxyuridine uptake. Western blot analysis revealed a remarkable increase of GFAP expression in GFC6-5 and GFC6-6 compared with that in NeoC6 and C6, in contrast to similar vimentin expression in all cell lines. The results indicate that the expression of GFAP has dramatic effects on cell morphology and cell growth suppression in C6 cells, suggesting that GFAP may function as a tumor suppressor in astrocytoma.     

Decrease of Glial Fibrillary Acidic Protein in Rat Frontal Cortex Following Aluminum Treatment

Aluminum lactate was injected either intraperitoneally or stereotactically into the lateral cerebral ventricles of rats. Rats were killed at various times after treatment, and frontal cortex, hippocampus, and striatum were dissected out. Microtiter plate-based sandwich ELISA and immunohistochemistry were used to measure the glial fibrillary acidic protein (GFAP) concentration. GFAP levels were significantly decreased in frontal cortex 7 days after a single lateral ventricular injection of aluminum lactate and 14 days following systemic treatment. In contrast, neither hippocampus nor striatum exhibited any significant changes in the content of this astrocytic intermediate filament protein after aluminum treatment. Levels of a predominantly astroglial enzyme, glutamine synthetase, were also selectively reduced in the frontal cortex following intraventricular injection of aluminum. This depression exhibited a regional and temporal specificity similar to that found for GFAP. These results suggest a selective and progressive diminution of astrocytic responsivity in frontal cortex following either systemic or intraventricular aluminum dosing. The depression of GFAP levels reported here, which was found in the rat cerebral cortex 7-14 days after aluminum treatment in a species that does not form neurofilamentous aggregates, may reflect extended impairment of astrocytic function and suggests that these cells may be the primary targets of aluminum neurotoxicity.     

Distribution of Glial Fibrillary Acidic Protein in Gliosed Human White Matter

Glial fibrillary acidic protein (GFAP) in gliosed white matter from multiple sclerosis plaques and cerebral infarcts was examined by polyacrylamide gel electrophoresis and immunoblotting. Using a monoclonal antibody raised against human GFAP, up to 11 GFAP polypeptide bands of molecular weight 37-49 kilodaltons were identified in particulate and supernatant fractions of CNS tissue homogenates. Soluble GFAP constituted about one-quarter of the total GFAP in normal cerebral white matter. In brain lesions in which reactive astrocytes were observed microscopically, the proportion of soluble GFAP was increased, with a greater representation of the lower-molecular-weight forms. In brain chronic sclerotic plaques, almost all of the GFAP was in the particulate form. Purified particulate GFAP was susceptible to proteolysis at acid but not at neutral pH in the presence of CNS homogenates. In tissue autolysis studies, GFAP was stable in situ for periods well in excess of average CNS postmortem times.     

Tumor Necrosis Factor-α and Basic Fibroblast Growth Factor Decrease Glial Fibrillary Acidic Protein and Its Encoding mRNA in Astrocyte Cultures and Glioblastoma Cells

Abstract: Tumor necrosis factor-α is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-α. Treatment with tumor necrosis factor-α for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-α treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-α, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-α induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-α. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-α treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.     

Rapid Increases in Glial Fibrillary Acidic Protein mRNA and Protein Levels in the Copper-Deficient, Brindled Mouse

The brindled mouse (MObr/y) carries an X-linked mutation that produces severe copper deficiency. Affected males suffer profound deficits in oxidative metabolism. We have examined astrocyte pathology in MObr/y during development and have found marked changes in the metabolism of glial fibrillary acidic protein (GFAP). Immunocytochemistry with anti-GFAP antisera revealed a marked increase in staining at postnatal day 12 (P12), compared to heterozygous female and unaffected male littermates, particularly in neocortex and thalamus. Septum, hypothalamus, and striatum showed little change. Western blot analysis revealed increased levels of GFAP in MObr/y forebrain and cerebellum. Levels of GFAP mRNA were determined by Northern blotting with a mouse GFAP cDNA probe. At P10, mRNA levels were normal, but increased to 8-10 times normal by P12. Levels at P15 remained similarly elevated. Thus, immunostaining and protein determinations correlate with mRNA elevations. Astrocytes can alter GFAP mRNA and protein levels over a relatively short time. Counts of neocortical cells did not reveal differences in cell numbers between MObr/y and controls, indicating that the observed changes reflect increased cellular levels and not a large increase in the numbers of astrocytes.     

Changes in the Solubility of Glial Fibrillary Acidic Protein After Ischemic Brain Damage in the Mouse

Abstract: In the present study, changes in the content of glial fibrillary acidic protein (GFAP) in mouse cortex were investigated at different time intervals after unilateral middle cerebral artery occlusion. The GFAP content was assessed semiquantitatively by ELISA and immunoblotting. GFAP immunoreactivity was determined for each animal separately in protein fractions obtained from the ipsilateral, lesioned cortex and the contralateral, unlesioned cortex. Changes in the GFAP content of the lesioned cortex with respect to that of the unlesioned cortex were calculated for each fraction individually. GFAP was detectable in all protein fractions with a significant amount recovered from the aqueous extracts. A pronounced increase in the GFAP content of the lesioned cortex was observed. As measured by ELISA, this increase was maximal 5 days after injury and significantly more pronounced for the soluble and the Triton X-100-soluble protein fractions (mean increase 7 days after lesion, 281.4 and 240.2%, respectively) than for the crude cytoskeletal fraction (mean increase, 153.3%). A small and transient increase in GFAP immunoreactivity was also found in all protein fractions prepared from the contralateral, unlesioned cortex. These results were confirmed by immunoblotting.     

Analysis and Comparison of In Vitro Synthesized Glial Fibrillary Acidic Protein with Rat CNS Intermediate Filament Proteins

Intermediate filament (IF) proteins from rat spinal cord were analyzed by two-dimensional gel electrophoresis and compared with the in vitro translation products of a messenger RNA-dependent reticulocyte lysate system stimulated with 16-day-old rat brain polysomes. In two dimensions, the molecular weight 49,000 to 50,000 band of the IF preparation resolved to seven spots, whereas antiserum to glial fibrillary acidic (GFA) protein precipitated only two immediately adjacent radiolabeled in vitro synthesized products, with molecular weights of 49,000 to 50,000. Autoradiographs of two-dimensional gels of extracted IF proteins incubated with iodinated IgG fraction of GFA protein antiserum showed that all seven spots were recognized by the antiserum. These observations suggest that the primary gene product of GFA protein is modified either by post-translational processing or experimental artifact.