nmhaFGF对大鼠肾脏缺血-再灌注ET-1和NO的影响

目的 探讨不同浓度非促分裂人酸性成纤维细胞生长因子(nmhaFGF)对肾脏缺血-再灌注(I-R)损伤后内皮素1(ET-1)和一氧化氮(NO)含量的影响.方法 成年SD大鼠35只随机分为假手术(切除左肾,暴露右肾)(SA)组和4个模型组(切除左肾,右肾动静脉夹闭60 min).建模后5 min经舌静脉注射nmhaFGF 10 μg/kg(A组)、20μg/kg(B组)、40μg/kg(C组)或生理盐水1.5 ml(D组).术后24 h处死,放射免疫及生化方法检测肾组织和血浆ET-1和NO含量.结果 B组皮质和外髓ET-1含量明显低于D组(P<0.05),C组肾皮质、外髓、内髓和血清中ET-1含量都明显低于D组(P<0.01);B、C组肾组织中NO含量明显高于D组(P<0.05).结论 nmhaFGF可以通过降低ET-1和升高NO水平减轻大鼠肾脏I-R损伤.     

重组人酸性成纤维细胞生长因子的稳定性研究

目的研究重组人酸性成纤维细胞生长因子(rhaFGF)在不同温度下的存放稳定性。方法rhaFGF冻干粉和溶媒在4,25和37℃分别保存30个月;rhaFGF液体在4℃保存56d,在25和37℃分别保存35d。采用MTT法测定rhaFGF的生物活性,同时进行外观性状、水分含量、pH值的测量和无菌试验。结果4℃时,rhaFGF冻干粉、液体和溶媒的各项性质在观察期内都无变化。25℃时,rhaFGF冻干粉、液体的生物活性分别在存放18个月和35d有下降趋势。37℃时,rhaFGF冻干粉、液体的生物活性分别在存放12个月和35d有下降趋势。结论rhaFGF冻干粉在4℃时可有效保存2年;rhaFGF冻干粉溶解后于4℃时保存28d内使用有效;溶媒在4℃时保存2年质量稳定。     

重组人碱性成纤维细胞生长因子对大鼠动脉内皮损伤后再狭窄的影响

目的：探讨重组人碱性成纤维细胞生长因子（rh-bFGF)对经皮冠状动脉腔内成形术后再狭窄的预防效果。方法：用2F球囊导管造成大鼠左颈总动脉内皮损伤。治疗组每天im rh-bFGF 10kU/kg.分别于术后7天和14天,每组各处死大鼠10只,取左颈总动脉进行[^3H]胸腺嘧啶掺入测定和病理形态学检查。结果：在第7天和第14天时,与模型对照组相比,rh-bFGF治疗组颈总动脉平均新生内膜厚度明显变薄;平均中膜面积缩小;平滑肌细胞和弹力板层数减少;胶原含量及[^3H]胸腺嘧啶掺入量也比模型对照组明显降低。结论：适当应用rh-bFGF有抑制气囊损伤后动脉新生内膜增厚,降低再狭窄发生的作用。     

重组人酸性成纤维细胞生长因子C-末端测序

目的：应用蛋白质N-末端序列分析仪测定重组人酸性成纤维细胞生长因子（aFGF）C-末端氨基酸序列。方法：应用多肽分析软件选择合适的蛋白内切酶完全酶切aFGF，酶切后用RP—HPLC进行分离，收集软件预测C-末端肽段保留时间处的肽段峰，用蛋白质N-末端序列分析仪直接测得该肽段氨基酸全序列。结果：实测肽图图谱与软件预测理论图谱一致，所得到的肽段为aFGF C-末端肽段，经测序其结果与理论序列完全一致。结论：通过选择合适的蛋白内切酶，可运用RP—HPLC和蛋白质N-末端序列分析仪测定基因工程产品C-末端氨基酸序列。     

重组人碱性成纤维细胞生长因子Ⅳ期临床试验观察

目的　进一步考察重组人碱性成纤维细胞生长因子 (rh- b FGF)的疗效、不良反应和适应症 ,并做出安全性和有效性的评价。方法　采用开放临床试验。结果　浅 度创面 7d愈合率 94.43 %± 7.83 % ,平均愈合时间 7.83± 1 .3 4 d。深 度创面 1 5 d愈合率 88.0 5 %± 1 7.6 1 % ,平均愈合时间 1 5 .40± 3 .5 8d。结论 :rh- b FGF能有效促进 度烧、烫伤创面的愈合 ;用药过程未发现对心、肝、肾等重要脏器损害及不良反应     

碱性成纤维细胞生长因子在肺鳞癌与肺腺癌组织中的表达

目的 探讨碱性成纤维细胞生长因子(bFGF)在肺鳞癌、腺癌组织中的表达及其与肿瘤微血管生成的关系.方法 免疫组化法检测76例肺癌标本(肺鳞状细胞癌31例、肺腺癌45例)bFGF的表达及以CD34衡量的微血管增生情况.结果 在76例标本中,53.9%的肿瘤组织标本检测到bFGF阳性表达,与TNM分期及淋巴结转移相关;同时发现肿瘤组织中微血管增生程度亦与肿瘤的TNM分型和淋巴结转移相关.结论 bFGF分子在肺癌发生、发展中具有重要作用.     

单次血液灌流对成纤维细胞生长因子23的影响

目的 观察单次血液灌流治疗对成纤维细胞牛长因子23(FGF-23)的影响.方法 对19例维持性血液透析期患者进行血液灌流串联血液透析联合治疗,观察单次血液灌流对FGF-23的清除效果.结果 单次血液灌流2 h可明显降低血FGF-23水平[(624.2±50.9)Pg vs.(823.7±81.6)pg](P＜0.01).单根血液灌流器治疗2 h后仍有吸附作用,与2 h比较,4 h FGF-23浓度明显降低[(576.4±47.0)Pg vs.(624.2±50.9)pg](P＜0.01).结论 血液灌流可有效降低FGF-23水平.     

Basic fibroblast growth factor enhanced LAK cell cytotoxicities against human bladder neoplasm cells 1

目的：探讨白细胞介素Ⅱ（ＩＬ２）和碱性成纤维细胞生长因子（ｂＦＧＦ）对膀胱癌患者淋巴因子激活的杀伤细胞（ＬＡＫ细胞）的作用．方法：用细胞计数观察不同浓度ｂＦＧＦ对ＬＡＫ细胞增殖的影响．以膀胱癌细胞系ＥＪ及新鲜分离患者自体肿瘤细胞（ＢＴＣ）为靶细胞,用ＭＴＴ法测定ＬＡＫ细胞对膀胱癌细胞的细胞毒作用．结果：虽然外周血单核细胞（ＰＢＭＣ）的增殖可被ｂＦＧＦ５μｇ·Ｌ－１所抑制,ＩＬ２所诱导的ＬＡＫ细胞的增殖却不受ｂＦＧＦ的影响,ｂＦＧＦ明显加强ＬＡＫ对ＥＪ细胞和ＢＴＣ的细胞毒作用．结论：虽然ｂＦＧＦ抑制ＰＢＭＣ的增殖,但ｂＦＧＦ又增强膀胱癌患者ＬＡＫ细胞对肿瘤细胞的细胞毒性．     

Effects of basic fibroblast growth factor on central nervous system functions.

Basic fibroblast growth factor (bFGF), initially identified as mitogens with prominent angiogenic properties, is now recognized as multifunctional growth factors with notable actions on neuronal cells. bFGF promotes the survival and neurite growth of brain neurons in vitro and in vivo, suggesting that it functions as a neurotrophic factor. This effect of bFGF could be beneficial for improving the survival of grafted neurons in transplantation. Furthermore, bFGF acutely modulates synaptic transmission in the hippocampus, suggesting that it has a role like a neurotransmitter or neuromodulator. In this article, we make a brief review of multiple biological activities of bFGF for brain neurons and discuss its potential usefulness for the treatment of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease.     

重组人碱性成纤维细胞生长因子对烧伤创面修复作用的疗效观察

目的　观察重组人碱性成纤维细胞生长因子 (rh- b FGF)的疗效、适应症及不良反应。方法　采用多中心随机对照和开放临床试验 ,选择同体同深度、相近或对称部位的烧伤创面、肉芽创面进行随机自身对照试验 ,部分患者采用开放试验。结果　对于浅 度、深 度及慢性肉芽创面 ,较对照组愈合时间缩短。结论　rh- b FGF能有效促进浅 度、深 度烧伤创面及慢性肉芽创面的愈合 ,且无明显不良反应及毒副作用。     

重组人酸性成纤维细胞生长因子治疗重型口腔溃疡的临床疗效观察

目的 评价酸性成纤维细胞生长因子(促溃疡愈合药)治疗重型口腔溃疡临床疗效.方法 收集口腔深溃疡患者97例,其中包括重型复发性阿弗他溃疡(MaRAU)患者63例,随机分为3组,分别用封闭治疗、局部用药、封闭及局部用药联合的治疗方法;另有创伤性溃疡34例,随机分为2组:对照不经药物治疗.治疗组局部用药治疗.结果 察患者疼痛时间,其中MaRAU患者中,封闭疗法组与局部用药组有显著性差异;封闭疗法组与结合疗法组无显著性差异;局部用药组与结合疗法组有显著性差异.创伤性溃疡患者中,对照组与用药组无显著性差异.溃疡愈合后,评价平均溃疡期以及是否留有瘢痕:MaRAU及创伤性溃疡患者中,各组间均有显著性差异.结论 单用药外用可以促进溃疡愈合,但疼痛缓解作用较弱.局部封闭与用药结合疗法对重型溃疡疗效显著.     

Effects of pH and polyanions on the thermal stability of fibroblast growth factor 20

Fibroblast growth factor 20 (FGF20) is a member of the FGF family with potential for use in several different therapeutic categories. In this work, we provide the first structural characterization of FGF20 using a wide variety of approaches. Like other members of the FGF family, FGF20 appears to possess a beta-trefoil structure. The effect of pH on the conformation and thermal stability of FGF20 is evaluated using far-UV circular dichroism (CD), intrinsic and ANS fluorescence, and high-resolution derivative UV absorption spectroscopy. Empirical phase diagrams are constructed to describe the solution behavior of FGF20 over a wide pH and temperature range. The protein appears to be unstable at pH <5, with aggregation and precipitation observed during dialysis. A major heat-induced conformational change also causes aggregation and precipitation of FGF20 at elevated temperatures. The highest thermal stability is observed near neutral pH (Tm ~55 degrees C at pH 7). The effect of several high- and low-molecular mass polyanions on the thermal stability of FGF20 is also examined using CD, intrinsic fluorescence, and DSC analysis. Among these ligands, heparin exhibits the greatest stabilizing effect on FGF20, increasing the Tm by more than 10 degrees C.     

Noninvasive transdermal iontophoretic delivery of biologically active human basic fibroblast growth factor

Human basic fibroblast growth factor (hbFGF; 17.4 kDa) has shown promise in the treatment of several dermatological conditions; symptomatic improvement was also observed in patients with peripheral arterial disease after arterial infusion. The objective of this study was to demonstrate the feasibility of using transdermal iontophoresis to deliver biologically active hbFGF noninvasively into and across the skin. The protein was cloned, expressed and purified in-house. Porcine skin was used to investigate transdermal iontophoretic transport of hbFGF as a function of current density (0.15, 0.3, and 0.5 mA/cm(2)); results were subsequently confirmed using human skin. Cumulative hbFGF permeation and skin deposition were quantified by ELISA. The absence of proteolytic degradation during skin transit was confirmed by SDS-PAGE. Biological activity postdelivery was determined using cell proliferation assays in human foreskin fibroblast (HFF) and NIH 3T3 cell lines. Confocal laser scanning microscopy (CLSM) was used to visualize the distribution of rhodamine-tagged hbFGF in the skin. Cumulative iontophoretic permeation at 0.3 mA/cm(2) was statistically superior to that at 0.15 mA/cm(2); however, there was no further improvement at 0.5 mA/cm(2). Significant skin deposition of hbFGF was observed, and this dominated transport; for example, after iontophoresis for 8 h at 0.5 mA/cm(2), skin deposition (77.74 ± 37.36 μg/cm(2)) was 4.4-fold higher than cumulative permeation (17.64 ± 5.18 μg/cm(2)). The superior skin deposition may be advantageous for dermatological applications. The HFF and NIH 3T3 cell proliferation assays confirmed that biological activity of hbFGF was retained postdelivery. Coiontophoresis of acetaminophen showed that the dominant transport mechanism switched from electroosmosis to electromigration upon increasing current density from 0.15 to 0.3 mA/cm(2). Experiments using human skin confirmed that iontophoretic permeation of hbFGF across porcine and human membranes was statistically equivalent. CLSM images of rhodamine-tagged hbFGF postiontophoresis indicated that the protein was evenly distributed throughout the epidermis and dermis. In conclusion, the results confirmed that transdermal iontophoresis was indeed able to deliver structurally intact, functional hbFGF noninvasively into and across the skin. The amounts of protein delivered were similar to those in reports from preclinical and clinical studies.     

冻干重组碱性成纤维细胞生长因子无人血清白蛋白保护剂的研究

目的在冻干重组碱性成纤维细胞生长因子制剂中引入一种无人血清白蛋白保护剂。方法采用 3种药用辅料按一定比例配制保护剂。结果加入无人血清白蛋白保护剂的 3批供试品 ,成品各项检查均合格。生物效价在 (40± 2 )℃、(2 5± 2 )℃、2℃～ 8℃保存分别达 6、12、3 0个月。结论在重组碱性成纤维细胞生长因子冻干制剂中无人血清白蛋白保护剂可以替代人血清白蛋白     

重组人酸性成纤维细胞生长因子Ⅰ期临床研究

目的:确定人体对重组人酸性成纤维细胞生长因子(rhaFGF)的耐受性程度并研究其在人体的药动学特性.方法:将36例深Ⅱ°烧伤患者随机分为5组,分别在创面滴注不同剂量的rhaFGF(25,50,100,200和300 U·cm-2),qd,直至创面愈合,或用至21 d.比较各组创面愈合时间和愈合率,定期测定体温、脉搏、血压、呼吸及血尿常规、肝肾功能.并用ELISA方法测定血清rhaFGF的浓度.结果:除4例发生局部疼痛外,各剂量组均未见明显不良反应;该药很少经表皮创面吸收进入血液,各剂量组在用药后不同时间点均未能在血清中测到rhaFGF;各剂量组创面愈合时间以100U·cm-2剂量组最短.结论:rhaFGF按剂量25,50,100,200和300U·cm-2用于烧伤患者是安全的,以100U·cm-2剂量组创面愈合所需时间最短.推荐Ⅱ期临床试验中使用剂量为100U·cm-2.     

酸性成纤维细胞生长因子的生物学特性

酸性成纤维细胞生长因子作为成纤维细胞生长因子家族的成员之一,不但具有促使DNA的合成、细胞分裂和分化等促分裂活性,而且还具有舒张血管、缺血保护、神经调节和保护等内分泌激素样活性。促分裂活性与其多肽的三维结构紧密相关,其中受体结合区、核转位区和肝素结合区在促分裂活性中具有重要地位。对于酸性成纤维细胞生长因子具有的内分泌激素样活性也与其蛋白质结构有关     

Therapeutic utilities of fibroblast growth factor 19

Introduction: Diabetes and associated metabolic conditions have reached pandemic proportions worldwide and there is a clear unmet medical need for new therapies that are both effective and safe. FGF19 is a distinctive member of the FGF family that functions as an endocrine hormone.

Areas covered: An up-to-date report on the exciting findings related to the involvement of FGF19 in the regulation of glucose, bile acid metabolism and energy expenditure. The role of FGF receptors in these different activities. The therapeutic potential of FGF19 and the engineering opportunities for removing undesirable mitogenic activity.

Expert opinion: The ability of FGF19 to regulate bile acid homeostasis, gallbladder filling and tumor development and its potent ability to normalize glucose, lipid and energy homeostasis have made it a potential therapeutic target for the treatment of patients with gallstones, cancer and metabolic diseases, among others. Its potential utility as a novel therapeutic for both type 1 and type 2 diabetes is of particular interest. The ability to separate the undesired mitogenic activity from its potent metabolic activities has opened new opportunities for the development of potential therapeutic molecules based on FGF19 in treating various conditions associated with metabolic syndrome.     

Therapeutic utilities of fibroblast growth factor 19

INTRODUCTION: Diabetes and associated metabolic conditions have reached pandemic proportions worldwide and there is a clear unmet medical need for new therapies that are both effective and safe. FGF19 is a distinctive member of the FGF family that functions as an endocrine hormone. AREAS COVERED: An up-to-date report on the exciting findings related to the involvement of FGF19 in the regulation of glucose, bile acid metabolism and energy expenditure. The role of FGF receptors in these different activities. The therapeutic potential of FGF19 and the engineering opportunities for removing undesirable mitogenic activity. EXPERT OPINION: The ability of FGF19 to regulate bile acid homeostasis, gallbladder filling and tumor development and its potent ability to normalize glucose, lipid and energy homeostasis have made it a potential therapeutic target for the treatment of patients with gallstones, cancer and metabolic diseases, among others. Its potential utility as a novel therapeutic for both type 1 and type 2 diabetes is of particular interest. The ability to separate the undesired mitogenic activity from its potent metabolic activities has opened new opportunities for the development of potential therapeutic molecules based on FGF19 in treating various conditions associated with metabolic syndrome.     

碱性成纤维细胞生长因子表达及手术方式对翼状胬肉手术后复发的影响

目的 探讨碱性成纤维细胞生长因子(bFGF)在翼状胬肉的表达及手术方式对翼状胬肉手术后复发的影响.方法 98例初发型翼状胬肉患者(107眼)随机分成两组,50眼行翼状胬肉单纯切除术(单纯切除组),57眼行翼状胬肉切除联合角膜缘干细胞移植术(干细胞移植组);免疫组织化学SP法检测翼状胬状组织bFGF表达.结果 bFGF在翼状胬肉的表达明显高于正常结膜(P<0.01);干细胞移植术组术后复发率明显低于单纯切除术组(15.8%vs.28.0%)(P<0.01),且复发时间明显推迟[(13.6±4)个月vs.(7.4±2)个月](P<0.01);bFGF表达量高的患者手术后复发率明显高于表达量低的患者(24.6%vs.18.8%)(P<0.01).结论 bFGF表达强度可作为预测手术后复发的危险因素;胬肉切除联合角膜缘干细胞移植术可降低术后复发率.     

重组人碱性成纤维细胞生长因子对大鼠和小鼠急性炎症的影响(英文)

目的:研究重组人碱性成纤维细胞生长因子的抗炎作用。方法:用巴豆油致小鼠耳肿,角叉菜胶致小鼠足肿,致小鼠、大鼠急性腹膜炎模型,观察rh-bFGF对小鼠耳肿胀、足肿胀、腹腔渗液中蛋白含量以及大鼠腹腔渗液中白细胞数、蛋白含量、超氧化酶歧化酶活性、β-N-乙酰氨基葡萄糖苷酶释放、一氧化氮含量、一氧化氮合酶活性、丙二醛和前列腺素E_2生成的影响。结果:rh-bFGF2,4kU/kg im明显抑制小鼠耳肿、足肿和腹腔中蛋白渗出;rh-bFGF4kU/kg im明显抑制大鼠腹腔中白细胞游走、蛋白渗出,降低腹腔渗液中MDA含量,升高SOD活性,明显降低NOS活性、NO和PGE_2含量。但rh-bFGF对腹腔渗液中NAG的升高无明显影响。结论:rh-bFGF肌注有抗炎作用,可能与降低毛细血管通透性,抑制白细胞游走,降低NO、MDA和PGE_2含量,清除自由基有关。