胰岛素样生长因子——Ⅰ在胎儿肝、肾等组织的分布

目的　研究胰岛素样生长因子 (IGFs)对胎儿组织增殖和分化的作用。方法　应用免疫组化 ABC法对16至 2 4周胎龄肝、肾、肾上腺、脾、胸腺等组织 IGF— I阳性细胞进行定位研究。结果　胎儿期内 ,以上器官中均有IGF— I阳性细胞存在 ,不同个体和器官其阳性细胞的数量、反应强弱和表达情况有差异。结论　在人胎发育过程中 ,这些器官组织均能表达 IGF— I,对其增殖分化起着自分泌和旁分泌的作用     

胰岛素样生长因子—Ⅰ在胎儿肝、肾等组织的免疫组化研究

胰岛素样生长因子 (Insulin- LikeGrowth Factor,IGFs)对胎儿组织增殖和分化起着十分重要的作用。本文应用免疫组化 ABC法对 16至 2 4周胎龄肝、肾、肾上腺、脾、胸腺等组织 IGF- 阳性细胞进行定位研究。结果显示 :在胎儿期内 ,以上器官中均有 IGF- I阳性细胞存在 ,不同个体和器官其阳性细胞的数量、反应强弱和表达情况有差异。结果提示 ,在人胎发育过程中 ,这些器官组织均能表达 IGF- ,对其增殖分化起着自分泌和旁分泌的作用。     

胰岛素样生长因子Ⅰ、胰岛素样生长因子Ⅰ受体在大肠癌中的表达及其意义

目的检测胰岛素样生长因子Ⅰ（IGF-Ⅰ）、胰岛素样生长因子Ⅰ受体（IGF-ⅠR）蛋白在大肠癌中的表达,并分析与临床病理学因素的关系．探讨两者在大肠癌发病机制中的相互作用及与患者预后的关系。方法选取不同类型的大肠癌组织48例（试验组）,其中男性25例,女性23例：年龄34～78岁,平均年龄53岁。任意选癌旁5cm以上的正常组织24例（正常对照组）。采用SABC法检测IGF-Ⅰ、IGF-ⅠR的表达。结果在48例大肠癌组织中,IGF-Ⅰ、IGF-ⅠR的阳性表达率分别为64．58％、58．33％,均显著高于癌旁正常组织中的16．67％、16．67％。IGF-Ⅰ、IGF-ⅠR在大肠癌组织中的表达与肿瘤的浸润程度、淋巴结转移、Dukes’分期有关。而与其他的病理因素及患者5年生存情况无关。IGF-Ⅰ和IGF-ⅠR在大肠癌组织中的表达呈明显相关性。结论IGF-Ⅰ、IGF-ⅠR可能相互协同作用参与大肠癌的浸润、转移,可作为反映大肠癌进展的重要生物学指标．但IGF-Ⅰ、IGF-ⅠR阳性表达与大肠癌患者的预后无明显相关性。     

胰岛素样生长因子—Ⅰ

胰岛素样生长因子Ⅰ（ＩＧＦ－Ⅰ）参与体内多种细胞的生长和分化，与许多肿瘤细胞的发生和生长密切相关，实验表明乳腺癌、小细胞肺癌、星形细胞瘤等肿瘤中ＩＧＥ－Ⅰ水平异常。ＩＧＦ－Ⅰ可与癌基因相互作用，可相互调节其功能。ＩＧＦ－Ⅰ的表达分泌水平与免疫细胞的增殖和活化状态密切相关     

胰岛素样生长因子Ⅰ与胎儿生长受限的相关性研究

目的探讨胰岛素样生长因子-Ⅰ（IGF-Ⅰ）与胎儿生长受限（FGR）的相关性。方法采用放射免疫法和免疫放射法测定20例FGR孕妇（FGR组）和17例正常孕妇（对照组）的血清及新生儿脐血IGF-Ⅰ水平,并对其结果进行相关性研究。结果 FGR组孕妇血清IGF-Ⅰ（115.44±4.34）μg/L,低于对照组（121.92±10.51）μg/L（P〈0.01）,差异有统计学意义;FGR组脐血清IGF-Ⅰ（121.48±5.85）μg/L,低于正常组的（124.24±10.08）μg/L（P〈0.01）,差异有统计学意义;孕妇血清IGF-Ⅰ水平与新生儿出生体重无相关性（r=0.189,P〉0.05）。新生儿脐血IGF-Ⅰ水平与新生儿出生体重呈正相关（r=0.575,P〈0.05）。结论 IGF-Ⅰ可能在FGR的发病中有重要的作用,并可能为将来诊断和治疗FGR提供新的途径。     

胰岛素样生长因子及胰岛素样生长因子结合结白-3与胎儿生长发育的关系

目的探讨胰岛素样生长因子-Ⅰ、胰岛素样生长因子-Ⅱ、胰岛素样生长因子结合蛋白-3与胎儿生长发育的关系,为FGR的临床诊断和治疗提供理论依据和新思路。方法分别采集确诊FGR组、正常对照组和巨大儿组胎儿脐血标本,采用放射免疫测定其中胰岛素样生长因子-Ⅰ、胰岛素样生长因子-Ⅱ、胰岛素样生长因子结合蛋白-3的含量。结果 1.FGR组脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平下降,巨大儿组脐血清IGF-Ⅰ水平升高;2.新生儿脐血清IGF-Ⅰ、IGF-Ⅱ水平与新生儿出生体重、身长、胎盘重量呈明显正相关关系,脐血清IGF-Ⅰ水平与胎龄呈明显正相关关系,脐血清IGFBP-3水平与胎龄、新生儿出生体重、身长、胎盘重量呈明显正相关关系;3.脐血清IGF-Ⅰ与IG-FBP-3水平与产妇产前体重呈明显正相关关系,IGF-Ⅱ水平与产妇产前体重呈正相关关系。结沦脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平可作为预测胎儿和胎盘生长发育情况的参考指标,IGF-Ⅰ水平是其中最灵敏的指标;脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平的降低可能是导致FGR的重要原因之一;监测产妇产前体重可以间接反映胎儿血IGFs及IG-FBP-3水平,进而反映胎儿的生长发育状况。     

胰岛素样生长因子Ⅰ研究进展

本文介绍胰岛素样生长因子（ＩＧＦ－Ⅰ）的结构和生理作用及其在糖尿病治疗方面的应用。因ＩＧＦ－Ⅰ的降血糖作用可通过ＩＧＦ－Ⅰ受体介导，故对胰岛素受体缺陷和胰岛素抵抗患者可尝试应用，但长期使用的安全性和有效性尚需进一步研究。     

胰岛素样生长因子与胎儿生长发育的关系

为了探讨胎儿在宫内生长发育与胰岛素生长因子 -Ⅰ(IGF -Ⅰ )的关系及明确IGF -Ⅰ在胎儿生长发育中所起的作用 ,我们对不同体重的胎儿脐带血清做了IGF -Ⅰ浓度检测 ,以探讨其对胎儿体重的影响。材料和方法一、对象 :我院第一胎足月分娩健康产妇 71例所生产的健康新生儿 ,其母亲年龄 2 0～ 34岁 ,平均 2 6 2 5岁。将新生儿按出生时体重分为大、中、小三组 :其中体重≥ 4 0 0 0g为大体重组 ,有新生儿 11例 ;体重在 30 0 0～ 3999g为中体重组 ,有新生儿 37例 ;体重≤ 30 0 0g为小体重组 ,有新生儿 2 3例。二、方法 :离胎儿身体 2cm剪断脐…     

胰岛素-胰岛素样生长因子-Ⅰ与胎儿宫内生长发育的关系

目的探讨母血、脐血中胰岛素-胰岛素样生长因子的水平-Ⅰ与胎儿宫内生长发育的关系及意义。方法收集2010年9月～2011年3月在本院分娩的单胎足月正常妊娠(无产科并发症)孕妇及其新生儿各90例,分娩前抽取孕妇空腹静脉血5 ml,胎儿娩出后即抽脐静脉血5 ml,标本收集后用高效液相色谱法测定母血、脐血中胰岛素及胰岛素样生长因子-Ⅰ的水平。结果 SGA脐带血清胰岛素、胰岛素样生长因子-Ⅰ水平明显低于AGA、LGA;AGA脐血胰岛素、胰岛素样生长因子-Ⅰ水平低于LGA组,差异均有统计学意义;母血胰岛素样生长因子-Ⅰ水平在SGA、AGA、LGA三组中差异有显著性(P<0.01),而胰岛素水平在SGA、AGA、LGA三组中差异无显著性;脐血中胰岛素与胰岛素样生长因子-Ⅰ水平呈正相关关系;脐血胰岛素、胰岛素样生长因子-Ⅰ水平与新生儿出生体重、身长、胎盘重量、体重指数呈明显正相关关系。结论脐血胰岛素、胰岛素样生长因子-Ⅰ水平与胎儿生长发育相关,低脐血胰岛素、胰岛素样生长因子-Ⅰ水平与胎儿宫内生长受限关系更为密切,母血胰岛素样生长因子-Ⅰ水平可作为评估胎儿宫内生长发育的指标。     

大肠息肉和大肠癌中胰岛素样生长因子Ⅰ受体的表达及其意义

目的 研究胰岛素样生长因子Ⅰ受体(IGF-Ⅰ R)在大肠息肉和大肠癌中的表达及其意义.方法 搜集内镜黏膜切除术(EMR)或内镜黏膜下剥离术(ESD)完整切除并经病理证实的32例患者的共47个大肠息肉,包括炎性息肉、管状腺瘤、绒毛状腺瘤;另选12例正常结肠黏膜组织及20例结肠腺癌黏膜组织作为对照.用免疫组织化学方法检测IGF-Ⅰ R的表达,分析IGF-Ⅰ R的表达程度及其与大肠癌的相关性.结果 IGF-Ⅰ R在正常对照组、炎性息肉组、管状腺瘤组、绒毛状腺瘤组和大肠癌组5组病例间经Spearman双变量等级相关性分析,相关系数为0.574,差异有统计学意义(P<0.01).结论 IGF-Ⅰ R在正常组织、炎性息肉、管状腺瘤、绒毛状腺瘤、大肠癌中的表达依次增加.IGF-Ⅰ R在评价息肉处于黏膜增生-腺瘤-癌变的发展中起了重要的作用.     

Influence of Gender on Serum Growth Hormone, Insulin-Like Growth Factor-I and Its Binding Protein-3 during Aging

Purpose

The serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects.

Materials and Methods

Sixty healthy volunteers (male 35, female 25, 36-70 years) were divided into ≤ 50 and > 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay.

Results

IGF-I was shown to be negatively correlated with age (women r = -0.62, p < 0.001; men r = -0.38, p < 0.05), whereas there was no correlation between IGF-I and GH values. Women > 50 years showed a significant reduction in IGF-I values than women ≤ 50 years (p < 0.01). Women > 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 ± 0.039404) than men of same age group (0.228326 ± 0.050979, p < 0.01) and women ≤ 50 years (0.247667 ± 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women.

Conclusions

The influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age.     

Immunohistochemical Localization of Components of the Insulin-Like Growth Factor-System in Human Deciduous Teeth

To investigate the occurrence of components of the insulin-like growth factor (IGF) system during the resorption process of shedding human deciduous teeth, we investigated sections of 13 decalcified and paraffin-embedded deciduous teeth immunohistochemically with antibodies against IGF-I and -II, six IGF binding proteins (IGFBPs 1-6) and the IGF receptors IGFIR and IGF2R. The teeth were in different stages of resorption and all showed reparative cementum formation. It was found that acellular extrinsic fiber cementum, reversal lines and reparative cellular intrinsic fiber cementum were immunoreactive for both IGFs and various IGFBPs. Therefore, in human deciduous teeth, all subgroups of cementum, but not dentine, may represent sources of components of the IGF system. Odontoclasts did not carry IGFs or the IGF1R, but IGFBPs and the IGF2R. Therefore, these cells, in contrast to osteoclasts, may not respond to IGFs, but may be involved in the release and sequestration of IGFs from cementum during the resorption process. In contrast to odontoclasts, cementoblasts and periodontal ligament (PDL) fibroblasts carried IGF1R. The influence of the IGF system on the function of these cells with respect to periodontal matrix turnover and cementogenesis is discussed. On the behalf of the IGFBP immunoreactivities found, the PDL extracellular matrix can be considered to be a reservoir for IGF system components, where binding proteins may regulate IGF distribution and activity.     

Regulation of Insulin-Like Growth Factor-I (IGF-I) Delivery by IGF Binding Proteins and Receptors

Delivery of growth factors via the bloodstream for the treatment of various diseases is regulated in part by interactions with cell surface binding elements. Understanding the kinetics of growth factor binding and transport by cells would, therefore, be advantageous. This report quantifies the binding, internalization, and transport of insulin-like growth factor-I (IGF-I) across bovine aortic endothelial cells (BAEC) cultured in vitro. Binding analysis indicated that IGF binding proteins (IGFBPs), primarily localized with the extracellular matrix, were the primary IGF-I binding elements in our system, with twice as many binding sites (8.0 ± 1.9 × 10⁴ per cell) as IGF-I receptors (IGF-IR) (3.9 ± 0.6 × 10⁴ per cell). Internalization of IGF-I by IGF-IR, but not IGFBPs, was detected, however both receptor and IGFBP binding were shown to inhibit rather than enhance the transport of intact IGF-I, albeit in different ways. IGFBPs retained IGF-I in the apical region while IGF-IR binding led to protein degradation. Based on our computational modeling and experimental data, we hypothesize that IGFBPs could function as a reservoir for IGF-I, sequestering it for later release and transport, and that this reservoir function of the IGFBPs could be used to promote controlled localized delivery of IGF-I.     

良性前列腺增生患者IGF-1、IGFBP-3水平的探讨

目的：研究良性前列腺增生(BPH)患者血清胰岛素生长因子—1(IGF—1)及其结合蛋白—3(IGFBP—3)的水平，探讨IGF—1、IGFBP—3对揭示BPH病因及治疗方面的价值。方法：采用免疫放射分析法(IRMA)测定64例BPH患者血清中IGF—1、IGFBP—3水平，并以30例健康人作对照。BPH患者按照其前列腺总体积(PV)的大小分为3组。Ⅰ组：PV≤30ml，18例；Ⅱ组：PV31-50ml，24例；Ⅲ组：PV≥50ml，22例。结果：BPH组血清IGF—1、IGF-BP-3含量与健康组比较，差异均显著(p＜0．05)；相关检验均呈正相关，p＜0．05。结论：IGF—1、IGFBP—3的高低与前列腺增生的程度有关联，对BPH病因的揭示以及BPH的非手术治疗均有一定的临床价值。     

检测血清IGF-1和IGFBP-3对儿童生长激素缺乏症的诊断价值

目的：探讨血清胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)浓度在诊断生长激素缺乏症(GHD)患儿中的应用价值。方法：用免疫放射分析检测38例GHD患儿和42例对照儿童的血清IGF-1和IGFBP-3,同时进行生长激素(GH)激发试验,用化学发光法检测GH,对两组结果进行比较。结果：GHD组患儿IGF-1和IGFBP-3均显著低于对照组儿童,且在GH激发试验中,GH的增加值也明显低于对照组。结论：检测血清中的IGF-1和IGFBP-3,对诊断GHD儿童具有重要价值。     

抗人胎胰相关抗原单克隆抗体C1免疫组化研究

用人胎胰提取物免疫ＢＡＬＢ／ｃ小鼠，获得能稳定分泌ＩｇＧ２ａ单抗的杂交瘤细胞Ｃ１。免疫组化染色表明，Ｃ１与胎胰、胰腺癌、胃癌和大肠癌等组织有较强结合反应，与正常胰腺、十二指肠、胃、大肠等处的消化腺上皮细胞有轻度结合反应。初步表明，通过定量分析单抗，Ｃ１对消化道癌肿的诊断有一定参考价值。     

Immunohistochemical Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor in Canine Cutaneous Fibrosarcomas

The expression of five markers associated with tumour angiogenesis, proliferation and apoptosis was studied in 24 canine cutaneous fibrosarcomas. Tumours were assigned histological grades and were immunohistochemically evaluated for the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2). Additionally, intra-tumour microvessel density (iMVD) was assessed by immunohistochemical labelling for expression of von Willebrand factor (vWf) and tumour proliferation index (PI) was measured following labelling of Ki-67 antigen. Finally, tumour apoptotic index (AI) was determined by application of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP end-labelling method (TUNEL). VEGF and VEGFR-2 expression were detected in 22/24 (92%) and 24/24 (100%) of fibrosarcomas, respectively. There was correlation between VEGF and VEGFR-2 expression (r = 0.51) and between histological grade and PI (r = 0.82). A significant difference in PI between tumours of different histological grade was found (P < 0.05). The median PI in grade 2 and 3 tumours (30.6 and 54.7, respectively) was significantly higher than in grade 1 tumours (6.4). Therefore, only PI correlates significantly with the histological grade of canine cutaneous fibrosarcomas. The potential for autocrine activity for VEGF exists in canine cutaneous fibrosarcomas, as VEGF and VEGFR-2 expression was found in most tumours.     

Age-Related Differences in the Metabolism of Proteoglycans in Bovine Articular Cartilage Explants Maintained in the Presence of Insulin-Like Growth Factor I

Articular cartilage explants from bovine calf and steer were cultured for up to 19 days in medium with or without 20% fetal bovine serum (FBS) or insulin-like growth factor I (IGF-I). Lower concentrations of IGF-I were required for maximal stimulation of PG synthesis in calf than in steer. In calf, but not in steer, IGF-I was as effective as 20% FBS in stimulating PG synthesis. The stimulation by IGF-I or FBS was not accompanied at either age by alterations in the composition of the aggregating PGs nor by changes in the proportions of CS-rich and CS-poor PG subpopulations.

In calf, IGF-I and FBS did not markedly alter the rate of turnover of either the ³⁵S-PGs synthesized in vitro or the unlabeled PGs. In steer, explants cultured in the absence of IGF-I or FBS exhibited very fast rates of turnover and depletion of matrix PG with time; IGF-I and FBS were both effective in reducing the turnover rate of ³⁵S-PGs and unlabeled PGs and in preventing PG depletion.     

RNA干扰沉默IGFBP2基因表达抑制裸鼠移植瘤的生长

目的：应用RNAi技术沉默胰岛素生长因子结合蛋白2基因（IGFBP2）,探讨其对人胃癌移植瘤生长的影响。方法：合成靶向IGFBP siRNA的表达质粒,于雌裸鼠皮下种植SGC7901胃癌细胞,肿瘤长至一定大小时,随机分为重组质粒实验组（A）,阴性质粒对照组（B）及盐水对照组（C）,于肿瘤局部分别注射重组质粒、阴性重组质粒、生理盐水。每3d给药一次,共8次,3d测量一次肿瘤体积,22d后处死全部动物,取肿瘤,测其大小和瘤重,RT-PCR检测各组IGFBP-2的表达。结果：A组肿瘤瘤块的体积和重量明显小于B、C组（P〈0.05）,RT-PCR显示,A组IGFBP-2的表达明显低于B、C组（P〈0.05）,B、C组IGFBP-2的表达差异无显著性（P〉0.05）。结论：靶向IGFBP-2siRNA瘤内注射能显著地延缓胃癌细胞裸鼠皮下移植瘤的生长,可能通过抑制IGFBP-2基因表达的机制抑制细胞增殖。