神经生长因子在糖尿病足创面组织中表达相关性的研究进展

动物实验研究证实神经生长因子（NGF）促进创面组织血管生成、血管内皮细胞再生,促进缺血创面的愈合及糖尿病创面的愈合。通过NGF在糖尿病创面表达改变的研究,有助于NGF促进糖尿病创面愈合机制的探讨,为糖尿病足创面愈合提供新的理论依据。     

神经生长因子受体在垂体腺瘤中的表达

目的：探讨两种神经生长因子（ＮＧＦ）受体（ＴｒＫＡ和ｇｐ７５）在各类垂体腺瘤中的表达。方法：采用免疫细胞化学ＳＡＢＣ法,检测了４４例经病理证实的垂体腺瘤中两种ＮＧＦ受体的表达情况。结果：ＴｒＫＡ在垂体ＰＲＬ分沁腺瘤中的过度表达率６９．２％,而在其它类型垂体腺瘤中的过度表达率为１９．４％,两者比较差异有非常显著性（Ｐ〈０．００５）。ｇｐ７５在垂体ＰＲＬ分泌腺瘤中的过度表达率在４６．２％,而在其它类型     

龟板促进帕金森病大鼠黑质神经生长因子信号分子的表达

目的:进一步探讨神经生长因子(NGF)/酪氨酸受体激酶A(TrkA)通路是否为龟板抗帕金森病(PD)大鼠多巴胺能神经元凋亡中的机制.方法:采用大鼠左侧黑质致密带注射6-羟基多巴胺(6-OHDA,0 2%)2μl造成PD模型,同时设立龟板组、模型组和正常对照组,用免疫组织化学显色方法观察PD大鼠中脑黑质NGF、 TrkA和磷酸化的糖原合成酶激酶-3β(p-GSK-3β)阳性神经元数目.免疫印迹法检测NGF、 TrkA、 p-GSK-3β蛋白表达水平的变化.结果:免疫组织化学显色显示龟板组PD大鼠中脑黑质致密部NGF、 TrkA的阳性细胞数明显多于模型组.免疫印迹法结果显示龟板组PD大鼠中脑黑质致密部NGF、 TrkA的蛋白表达水平高于模型组.结论:龟板能上调6-OHDA诱导的PD大鼠中脑黑质NGF、 TrkA和p-GSK-3β的表达,这可能是其抗PD大鼠多巴胺能神经元凋亡的分子机制.     

负压伤口治疗对糖尿病足创面肉芽组织血小板源生长因子表达的影响

目的探讨负压伤口治疗技术(NPWT)的应用对糖尿病足肉芽组织血小板源生长因子(PDGF)表达的影响。 方法选取解放军白求恩国际和平医院2010年1月至2014年12月收治的40例糖尿病足患者,采用单纯随机抽样法将患者随机分为NPWT组(20例)和对照组(20例),NPWT组创面采用负压伤口治疗技术治疗,对照组采用传统纱布换药治疗。两组分别于治疗前及治疗第12天取创面肉芽组织2份,一份置于4%多聚甲醛溶液中保存,行苏木精－伊红(HE)染色和免疫组织化学染色,HE染色观察肉芽组织形成情况,免疫组织化学染色观察肉芽组织PDGF的表达情况,通过Motic Medical 6.0数码医学图像分析系统检测吸光度值对PDGF蛋白行定量分析。同时,另一份肉芽组织标本－80℃冰箱中保存,采用Western blot法检测PDGF蛋白表达量。数据应用SPSS 13.0软件进行分析,PDGF吸光度值及PDGF蛋白表达量比较采用两独立样本t检验。 结果两组治疗前HE染色可见炎症细胞多,成纤维细胞、新生血管形成较少;两组治疗第12天肉芽组织HE染色均可见新鲜肉芽组织的形成,表现为新生血管、成纤维细胞增多,但与对照组相比,NPWT组新生肉芽组织增多较为明显。免疫组织化学分析显示,两组治疗后均可见PDGF蛋白表达上调;NPWT组治疗第12天PDGF吸光度值(0.41±0.05)与治疗前(0.29±0.04)比较,差异有统计学意义(t＝8.63,P<0.05);对照组治疗第12天PDGF吸光度值(0.33±0.04)与治疗前(0.28±0.04)比较,差异也有统计学意义(t＝3.62,P<0.05);但是,NPWT组治疗前后PDGF吸光度变化值为0.13±0.05,与对照组治疗前后PDGF吸光度变化值(0.05±0.03)比较,差异有统计学意义(t＝5.89,P<0.05)。Western blot分析显示,NPWT组治疗第12天PDGF蛋白表达量为0.24 ±0.04,与治疗前PDGF蛋白表达量(0.11±0.03)比较,差异有统计学意义(t＝11.01,P<0.05);对照组治疗第12天PDGF蛋白表达量为0.17±0.03,与治疗前PDGF蛋白表达量(0.12 ±0.03)比较,差异亦有统计学意义(t＝6.06,P<0.05);但是,NPWT组治疗前后PDGF蛋白表达量的变化值为0.12 ±0.03,与对照组治疗前后PDGF蛋白表达量的变化值(0.05 ±0.02)比较,差异有统计学意义(t＝9.06,P<0.05)。 结论应用NPWT可明显促进创面肉芽组织PDGF表达上调,从而促进创面的愈合。     

神经生长因子受体在人脊髓创伤后的再表达

为了了解神经生长因子受体（NGFR）在受损脊髓内的表达情况，用免疫细胞化学方法，在18例脊髓创伤后存活2小时至28个月患者死后脊髓石蜡切片上进行了研究。结果表明：最早于创伤后第4天起，前角运动神经元再表达NGFR。创伤30天后，NGFR阳性运动神经元逐渐减少，但直至伤后28个月仍可见到。创伤后7小时至9周，后索内轴突也表达了NGFR，可能是脊神经节细胞NGFR的轴浆运输效应。此外，受损脊髓内微血管壁外层也呈NGFR阳性。创伤后运动神经元再表达NGFR，反映神经细胞对神经生长因子的需求增加，以维持创伤后神经生长因子依赖性神经元的生存。     

神经生长因子受体信号转导研究进展

神经生长因子(NGF)是一种多功能细胞因子。NGF通过与NGF受体(NGF receptor,NGFR)的结合发生相应的生物学效应。本文就NGFR结构及信号转导等方面的研究作一简要综述。     

神经生长因子及其受体在前列腺癌中的表达

目的探讨神经生长因子(nerve growth factor,NGF)及其受体TrkA、p75在前列腺增生和前列腺癌中的表达。方法采用免疫组织化学SABC法检测前列腺良性增生10例、高分化8例、中分化14例和低分化23例石蜡包埋组织中NGF和TrkA、p75的表达。结果NGF和TrkA在前列腺增生、高分化癌、中分化癌、低分化癌中的均有表达;而p75在前列腺增生全部表达、高分化癌(8/4)、中分化癌(14/6)、低分化癌(23/3)中的表达呈逐渐降低趋势,其差异有显著性(p<0.05),前列腺增生与高分化癌、中分化癌、低分化癌相比差异均有显著性(p<0.05)。结论NGF和TrkA的表达与前列腺增生和前列腺癌进展无关。p75与前列腺癌恶性进展有关,p75表达减少在前列腺癌过程中起着重要的作用。     

神经营养因子对颅脑损伤保护作用的研究进展

神经营养因子广泛存在于脑及周围神经系统.无论在体内或体外它们都能促进神经系统的发育,维持神经元的生长、存活与分化;并可影响神经系统的突触可塑性.神经营养因子通过激活其特异性高亲和力酪氨酸激酶受体自身磷酸化而进行信号传递.颅脑损伤可以诱导神经营养因子基因表达,从而对受损的神经元产生保护作用,促使神经元功能恢复.     

Axl基因在肿瘤进展中的作用

Axl (Anexelekto)为受体酪氨酸激酶亚家族成员之一,与配体Gas6结合可激活Axl的酪氨酸激酶活性,激活下游信号转导途径.参与细胞黏附与识别、细胞增殖、抗凋亡、凝血、炎症反应等过程.Axl基因异常表达在多种肿瘤的发生、发展过程中发挥重要作用,包括抑制肿瘤细胞凋亡,参与肿瘤性血管生成及侵袭等病理过程.     

Effects of LNG-IUS on nerve growth factor and its receptors expression in patients with adenomyosis

The levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in the treatment of dysmenorrhea associated with adenomyosis. However, the mechanism of pain relief of LNG-IUS in patients with adenomyosis is unclear. We aimed to investigate the effects of LNG-IUS on the expression of nerve growth factor (NGF) and its receptors, NGFR p75 and TrkA in patients with adenomyosis. Endometrial and myometrial tissues were prepared from 17 LNG-IUS-treated patients and 15 hormonally untreated patients who had undergone hysterectomies for adenomyosis. Immunohistochemistry with antibodies against NGF, NGFR p75, and TrkA, was performed. The expression of NGF, NGFR p75, and TrkA in endometrium and myometrium of LNG-IUS-treated patients was significantly decreased compared to those of hormonally untreated patients. Our findings may indicate that the suppression of NGF and its receptors by LNG-IUS is another possible mechanism of relieving pain in patients with adenomyosis.     

Human mast cells express functional TrkA and are a source of nerve growth factor

Mast cells are the principal effector cells in IgE-dependent hypersensitivity reactions. Despite reports that rodent mast cells proliferate in the presence of nerve growth factor (NGF), human mast cells reportedly do not respond to this factor. To determine if human mast cells express the NGF receptors, TrkA tyrosine receptor and the low affinity NGF receptor (LNGFR), we first analyzed the mRNA expression by RT-PCR of TrkA and LNGFR in a human mast cell line (HMC-1) and in human mast cells cultured in the presence of stem cell factor. Both HMC-1 and cultured human mast cells were found to express TrkA but not LNGFR. TrkA protein was demonstrated by Western blot analysis of HMC-1 lysates. Using flow cytometric analysis and mast cell tryptase as a mast cell marker, both HMC-1 cells and cultured human mast cells were shown to co-express tryptase and TrkA. Treatment of mast cells with NGF resulted in phosphorylation of TrkA on tyrosine residues as detected by immunoblotting with an antiphosphotyrosine antibody. Furthermore, NGF induced the immediate early gene c-fos in HMC-1 cells. HMC-1 cells and cultured human mast cells were also found to express NGF mRNA, and conditioned medium from HMC-1 cells stimulated neurite outgrowth from chicken embryonic sensory ganglia in culture. This effect was blocked by anti-NGF. Thus, mast cells express functional TrkA and synthesize NGF, suggesting a mechanism by which NGF may act as an autocrine factor for human mast cells, and by which mast cells and nerves may interact.     

负压伤口疗法对糖尿病足轻、中度缺血创面肉芽组织转化生长因子-β1表达的影响

目的探讨负压伤口疗法(NPWT)对糖尿病足轻、中度缺血创面肉芽组织转化生长因子-β1(TGF-β1)表达的影响。 方法选取2014年1月至2018年2月在解放军白求恩国际和平医院接受NPWT治疗的43例糖尿病足患者,据踝肱指数(ABI)分为中度缺血组23例(0.5≤ABI<0.7)和轻度缺血组20例(0.7≤ABI<0.9)。于治疗前及治疗14 d后分别取创面肉芽组织,标本分成3份,1份于4%多聚甲醛溶液中固定,4 ℃保存,标本收齐后行免疫组织化学染色,分析TGF-β1平均光密度;另外2份于液氮中转送至-80 ℃冰箱中保存,其中1份行Western blotting法,分析TGF-β1蛋白表达情况,另1份行Real-time PCR,分析TGF-β1 mRNA表达情况。2组间数据比较采用独立样本t检验。 结果经免疫组织化学染色分析TGF-β1表达,中度缺血组和轻度缺血组经14 d治疗后TGF-β1平均光密度均高于治疗前,差异有统计学意义(P值均小于0.05),且相较于中度缺血组变化幅度[(38.71±12.78)%],轻度缺血组[(63.09±10.96)%]升高幅度显著,差异均有统计学意义(t＝－6.66,P<0.05);经Western blotting法分析TGF-β1蛋白表达水平,中度缺血组和轻度缺血组经14 d治疗后TGF-β1蛋白表达均高于治疗前,差异均有统计学意义(P值均小于0.05),且相较于中度缺血组变化幅度[(50.31±25.64)%],轻度缺血组变化幅度[(85.44±27.78)%]升高幅度显著,差异有统计学意义(t＝－4.31,P<0.05);经Real-time PCR法分析TGF-β1 mRNA表达水平,中度缺血组和轻度缺血组经14 d治疗后TGF-β1 mRNA表达均高于治疗前,差异均有统计学意义(P值均小于0.05),且相较于中度缺血组变化幅度[(73.85±41.22)%],轻度缺血组[(129.78±36.71)%]升高幅度显著,差异有统计学意义(t＝－4.67,P<0.05)。 结论NPWT能促进糖尿病足轻、中度缺血创面肉芽组织TGF-β1的表达,且对糖尿病足轻度缺血创面肉芽组织TGF-β1表达的促进作用优于糖尿病足中度缺血创面。     

NGF对乳腺癌细胞系MDA-MB-231和MCF-7增殖和存活的影响

目的:研究神经生长因子(NGF)对乳腺癌细胞系MDA-MB-231和MCF-7细胞增殖与存活的影响。方法:运用免疫荧光方法检测NGF及其受体酪氨酸蛋白激酶A(TrkA)的表达;运用酶联免疫吸附测定(ELISA)方法检测细胞的NGF自分泌情况;运用蛋白质印迹(Western blotting)方法检测TrkA蛋白的表达情况;运用NGF阻断剂Ro 08-2750对细胞进行NGF剥夺,通过单核细胞直接细胞毒性测定法(MTT)检测细胞增殖的情况;运用流式细胞仪检测细胞凋亡情况以及细胞周期分布的变化。结果:2株乳腺癌细胞系均表达NGF及其受体TrkA,NGF阻断剂Ro 08-2750能够明显抑制2种细胞的增殖,并具有剂量依赖性;流式细胞仪显示Ro 08-2750处理的MDA-MB-231细胞和MCF-7细胞的S期细胞比例明显增加,G2/M期细胞比例明显降低,MDA-MB-231细胞出现凋亡峰。结论:NGF剥夺明显抑制乳腺癌细胞系MDA-MB-231和MCF-7的增殖,并引起MDA-MB-231细胞凋亡。     

Nerve growth factor signal transduction in human B lymphocytes is mediated by gp140trk

Nerve growth factor (NGF) plays an important role in the regulation of the immune system. Recent studies from this laboratory demonstrated the presence of functional NGF receptors on human B lymphocytes; in addition, NGF has been shown to enhance B lymphocyte proliferation. NGF caused both concentration- and time-dependent increases in tyrosine phosphorylation of five proteins of 140, 110, 85, 60 and 42 kDa, which were identified as phospholipase C-γ1, phosphatidylinositol-3 kinase and mitogen-activated protein kinase. To elucidate the contribution of the Trk family of tyrosine kinases to the phosphorylation events induced by NGF, we identified gp140^trk in human B cells and in human B cell lines. Analysis of specific gp140^trk immunoprecipitates indicated that addition of NGF to B cells induced a rapid increase in the tyrosine phosphorylation of gp140^trk and inhibition of this phosphorylation prevented the tyrosine phosphorylation of other proteins. These data identify the central role of gp140^trk in NGF signaling of human B lymphocytes.     

糖尿病足截肢平面及愈合因素的分析

目的探讨糖尿病足截肢平面和截肢后切口愈合的影响因素。方法收集1998年1月至2009年12月出院的82例糖尿病足截肢患者临床资料,分别分析糖尿病足截肢平面与病程、外周神经障碍、血管狭窄程度、Wagner分级、创面感染情况的相关性,以及截肢后切口愈合情况与年龄、围手术期血糖控制水平、血管狭窄程度、外周神经障碍、Wagner分级、创面感染情况的相关性。结果糖尿病足截肢平面的选择与病程、外周神经障碍、血管狭窄程度有关(P0.05);截肢后切口愈合情况与年龄、血糖控制水平及血管狭窄程度相关(P0.05)。结论糖尿病足截肢平面的选择应通过病程、外周神经病变和血管狭窄程度量化分析;高龄、围手术期血糖控制不佳及重度血管狭窄是糖尿病足截肢后切口愈合欠佳的主要因素。     

Efficacy of intralesional recombinant human epidermal growth factor in chronic diabetic foot ulcers

Abstract

Objective: The aim of this study was to explore the clinical effects of intralesional administration of an epidermal growth factor (EGF) up to complete wound closure. Methods: Seventeen diabetic patients with full-thickness lower extremity ulcers of more than 4 weeks of evolution were enrolled in the study. Mean ulcer size was 15.5 +/? 7.5?cm². Intralesional injections of 75?µg of Heberprot-P three times per week for 5–8 weeks were given up to complete wound healing. Results: Full granulation response was achieved in all patients in 32.4 +/? 6.6 days. Complete wound closure was obtained in 16 (94.1%) cases in 53.1 +/? 4.7 days. The most frequent adverse events were burning sensation, tremors, chills and pain at the site of administration. After 1-year follow-up, only one patient relapsed. Conclusions: Intralesional EGF administration up to complete closure can be safe, effective and suitable to improve healing of chronic diabetic foot ulcer (DFU).     

血清IGF-1和VEGF水平与糖尿病足关系的研究

目的研究糖尿病足患者血清IGF-1和VEGF水平与糖尿病足部溃疡或坏疽的关系。方法分别采用放射免疫分析法和定量双抗体夹心ELISA法检测23例糖尿病足患者血清IGF-1和VEGF水平,并与健康人和2型糖尿病患者进行比较。结果糖尿病足患者血清IGF-1和VEGF水平显著低于糖尿病患者和健康对照组(P<0.05)。结论生长因子IGF-1和VEGF是糖尿病足发生和发展的重要影响因素,IGF-1和VEGF水平低下可能是糖尿病足部溃疡经久不愈的重要原因。