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。     

IGF-Ⅰ、IGFBP-3诊断矮小儿童生长激素缺乏的价值

目的:探讨胰岛素样生长因子-Ⅰ ( IGF-Ⅰ)和胰岛素样生长因子结合蛋白-3 ( IGFBP-3)诊断矮小儿童生长激素缺乏的价值.方法:①对64例身材矮小患儿用精氨酸激发试验和左旋多巴激发试验检测其血清生长激素(GH)水平,两项药物激发试验GH峰值均＜10ng/ml诊断为生长激素缺乏(GHD组,40例),其中有一项激发试验GH峰值＞10ng/ml,即可确实诊断为特发性矮小症( ISS组,23例).选取45例健康儿童作为对照组.②用化学发光法检测血清IGF-Ⅰ和IGFBP-3水平.结果:①血清IGF-Ⅰ水平,GHD组为(80.35±32.46)ng/ml,ISS组为(123.26±62.13)ng/ml,正常对照组为(362.20±78.21)ng/ml;血清IGFBP-3水平,GHD组为(2.67±1.32)ng/ml,ISS组为(3.62±1.524)ng/ml,正常对照组(6.39±1.06)ng/ml.②GHD组和ISS组患儿血清IGF-Ⅰ和IGFBP-3水平显著低于健康对照组(P<0.05) ;GHD组比ISS组患儿血清IGF-Ⅰ、IGFBP-3水平减低有显著性差异(P<0.05).③按正常对照组x-2s作为临界值诊断GHD,IGF-Ⅰ的阳性率为95%; IGFBP-3的阳性率为92.5%;IGF-Ⅰ、IGFBP-3水平同时评价时,阳性率为87.50%.结论:IGF-Ⅰ、IGFBP-3检测可用于诊断身材矮小儿童的生长激素缺乏.     

胎儿宫内生长受限临床评价指标的相关研究

目的进一步探讨IGFs及IGFBP-3与胎儿生长发育之间的关系,及其在FGR发病中的作用,以期寻找到可用于FGR早期预测和诊断的有效辅助指标。方法分别采集确诊FGR组、正常对照组孕妇羊水、肘静脉血和胎儿脐血标本,采用放射免疫法分别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含量。结果 1.FGR组IGF-Ⅰ、IGF-Ⅱ水平在脐血清、母血及羊水标本中均明显下降;2.IGFBP-3含量在脐血和羊水中明显上升,但在母血中无显著差异;3.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;4.脐血清IGF-Ⅰ与IGFBP-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。结论脐血清IGF-Ⅰ、IGF-ⅡI、GFBP-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;IGF-Ⅰ、IGF-ⅡI、GFBP-3水平的降低可能是导致FGR的重要原因之一。     

宫内生长迟缓胎儿脐血IGF-Ⅰ及IGFBP-3水平观察

目的:探讨新生儿脐血中胰岛素样生长因子-Ⅰ(IGF-Ⅰ)和胰岛素样生长因子结合蛋白-3(IGFBP-3)水平与胎儿宫内生长发育的关系.方法:采用放射免疫分析,分别对出生时体重正常新生儿与宫内生长迟缓的低体重新生儿脐血的IGF-Ⅰ及IGFBP-3水平进行检测.结果:宫内发育迟缓组新生儿脐血的IGF-Ⅰ及IGFBP-3的含量明显低于正常对照组(P＜0.01),有显著差异性.结论::IGF-Ⅰ和IGFBP-3与胎儿宫内生长发育密切相关,对胎儿的宫内生长发育起着重要的调节作用.     

血清IGF-1和IGFBP-3在矮小症患儿中的诊断意义

探讨胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)在矮小症患儿诊断中的价值.对青春发育前矮小症患儿92例,健康儿童(对照组)48名,用精氨酸激发试验和胰岛素低血糖激发试验检测血清生长激素(GH)水平,并根据患儿GH峰值分为完全性生长激素缺乏(CGHD组,20例)、部分性生长激素缺乏(PGHD组,38例)、特发性矮小(ISS组,34例).采用CLIA检测血清IGF-1和IGFBP-3.对CGHD组、PGHD组、ISS组和对照组血清IGF-1和IGFBP-3水平进行两两比较发现,除PGHD组和ISS组间无显著性差异外(P＞0.05),均有显著性差异(P＜0.01).本文结果显示血清IGF-1和IGFBP-3检测对矮小症患儿有重要意义,可以作为确诊CGHD有价值的指标,但对于PGHD和ISS患儿则需结合GH激发试验加以鉴别.     

IGF-1、IGFBP-3、CEA和CA125联合检测对肺癌的诊断价值

目的 探讨胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)、CEA及CA125联合检测对肺癌诊断的临床价值.方法 采用化学发光法分别对77例肺癌患者和41名健康体检者血清IGF-1、IGFBP-3、CEA和CA125水平进行检测,并对检测结果进行对比分析.结果 肺癌组血清IGF-1水平明显高于健康对照组(P＜0.01),血清IGFBP-3水平明显低于健康对照组(P＜0.05);单项检测时IGF-1灵敏性为28.57％,CEA灵敏性为44.16％,CA125灵敏性为40.26％;三项指标联合检测时灵敏性为75.33％.结论 IGF-1有助于肺癌的诊断,IGF-1、CEA及CA125联合检测可显著提高肺癌检出率.     

心脏彩超联检血清cTnI、IGF-Ⅰ和IGFBP-3水平对先天性心脏病诊断的临床价值

目的:探讨了心脏彩超联检血清心特异性肌钙蛋白(cTnI)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)和胰岛素样生长因子结合蛋白-3(IGFBP-3)水平对先天性心脏病的诊断价值.方法:应用放射免疫分析和酶联法对32例先天性心脏病患者进行了血清cTnI、IGF-Ⅰ和IGFBP-3测定,并与35名正常健康人作比较.结果:先天性心脏...     

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。     

IGF-I与宫内发育迟缓及其结合蛋白的关系

目的：检测宫内发育迟缓（IUGR）儿脐血胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白-3（IGFBP-3）水平,分析这些指标的变化程度与胎儿期生长的关系。方法：将86例脐血标本分为IUGR（即小于胎龄儿）组和适于胎龄儿（AGA）组。采用放射免疫分析（RIA）测定IGF-I水平,免疫放射分析（IR-MA）测定IGFBP-3水平。两组间比较用t检验,两变量之间的关系采用相关回归分析。结果：与AGA组相比,IUGR组脐血IGF-I和IGFBP-3水平显著降低（P均〈0.01）;IGF-I、IGFBP-3均随胎龄及出生体重增加而增加（P均〈0.01）;IGFBP-3与IGF-I呈正相关（P〈0.01）。结论：脐血IGF-I和IGFBP-3的含量可作为判断新生儿生长发育程度的一项客观指标。     

测定IGF-1及其结合蛋白诊断生长激素缺乏症的价值

目的：探讨胰岛素样生长因子1（IGF-1）和胰岛素样生长因子结合蛋白3（IGFBP-3）诊断生长激素缺乏症的价值。方法：采用免疫放射分析（IRMA）分别检测32例生长激素缺乏症（GHD）、35例特发性矮小症（Idiopathic short-small syndrome,ISS）、30例健康儿童血清IGF-1和IGFBP-3水平,同时比较IGF-1和IGFBP-3诊断GHD敏感性、特异性和实验有效率。结果：GHD组、ISS组、正常对照组血清IGF-1和IGFBP-3水平,两两比较均有显著性差异（P〈0．01,P〈0．05）;IGF-1、IGFBP-3水平与GH激发试验中的GH峰值呈正相关（r=0.312、0.354,P〈0．05）;诊断GHD,IGF-1的特异性为82,9％,敏感性为68．8％;IGFBP-3的特异性为91．4％,敏感性为75．0％,两者比较无显著性差异（P〉0．05）。结论：IGF-1和IGFBP-3的检测可能可作为筛查和诊断GHD有价值的指标,血清IGF-1、IGFBP-3水平的检测可能可替代GH激发试验。     

IGF-I和IGF-IR在高氧致新生鼠慢性肺疾病中的动态表达及其作用

目的研究IGF-I、IGF-IR在高氧致新生鼠慢性肺疾病（CLD）中的表达及作用。方法将足月新生大鼠144只随机分为高氧组和空气组,分别于实验1d,3d,7d,10d,14d,21d应用免疫组化和RT-PCR技术检测IGF-I、IGF-IR的动态表达。结果CLD时IGF-I和IGF-IR呈动态变化,高氧组和空气组比较,在实验3d～10d IGF-I和IGF-IR表达明显降低（P〈0.05）,14d和21d表达明显增强（P〈0.05）。结论IGF-I和IGF-IR是肺泡发育的正向调节因子,与CLD时肺泡分隔受阻、肺泡成熟障碍和肺纤维化有关。     

Role of insulin-like growth factor I signaling in neurodegenerative diseases

Disturbed trophic support to neurons has long been considered a potential mechanism in neurodegeneration. Recent evidence indicates that intracellular trophic signaling may be compromised in several neurodegenerative diseases. Changes in the levels of insulin-like growth factor I (IGF-I), a trophic hormone with multiple neuroprotective actions, have recently been observed in several human neurodegenerative illnesses. Therefore analysis of IGF-I pathways could help provide greater insight into trophic disturbances to neurons. However, neurodegenerative diseases with similar clinical manifestations show either high or low levels of circulating IGF-I. This apparently puzzling observation can be explained if we consider that IGF-I input to target neurons is disrupted by either lower IGF-I availability or by reduced cell sensitivity to IGF-I. The latter disturbance may be associated with high IGF-I levels. We hypothesize that in the majority of neurodegenerative diseases compromised IGF-I support to neurons emerges as part of the pathological cascade during the degenerative process and contributes to neuronal demise. In addition, loss of IGF-I input to specific neuronal populations might be the cause of a small group of neurodegenerative diseases.Abbreviations AT Ataxia-telangectasia - A Amyloid- - IGF Insulin-like growth factor - IGFBP Insulin-like growth factors binding protein - IRS Insulin receptor substrate protein - LID Liver IGF-1 deficiency - SCA Spinocerebellar ataxia - TNF Tumor necrosis factor     

肝细胞生长因子和类胰岛素样生长因子对心肌干细胞的诱导作用

目的探讨肝细胞生长因子(HGF)和类胰岛素样生长因子(IGF1)在外能否诱导心肌干细胞(CSCs)发生增殖并向心肌细胞定向分化。方法组织贴块法分离培养心肌干细胞,免疫荧光技术鉴定c-kit和CD34表达,流式细胞仪分选纯化c-kit+细胞,CFDA SE荧光探针示踪培养检测细胞增殖特征。实验分为单纯心肌干细胞组和与心肌共培养组,分别用HGF和IGF1干预,倒置显微镜观察细胞不同时期数量与形态的变化,活细胞工作站观察CFDA SE示踪剂荧光强弱,采集图像,进行统计学分析。免疫荧光技术检测Nkx2.5、心肌肌钙蛋白T(cTnT)的表达。结果单纯心肌干细胞组,生长因子刺激后心肌干细胞数量与形态均无明显变化。与心肌共培养组,细胞均发生增殖与形态变化,Nkx2.5、cTnT阳性表达,有个别心肌干细胞分化为自发搏动的心肌细胞。结论心肌干细胞与心肌细胞共培养条件下,HGF和IGF1能够促进心肌干细胞增殖,联合作用能够诱导心肌干细胞向心肌细胞分化。     

Alterations in the insulin-like growth factor system during the menstrual cycle in normal women

Objectives: To evaluate the effects of endogenous estrogens and progestins on the IGF-system during the normal menstrual cycle in healthy premenopausal women not using contraceptive drugs. Methods: Nine women had fasting blood samples obtained at 2–3 days intervals during a 5 week study period. Plasma levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3, estradiol and progesterone were measured by radioimmunoassay (RIA) in each sample. IGFBP-3 was also evaluated by Western ligand blot (WLB) and immunoblot. Any differences between the menstrual phase (defined as day 1–5), follicular and luteal phases (separation based on plasma estradiol and progesterone values) were evaluated by the Friedman test. Results: A small but significant difference in plasma levels of IGF-I (P<0.01) and IGFBP-3 (P<0.05) measured by RIA between the three phases were seen with the highest levels found during the follicular phase. No change in plasma levels of IGFBP-1 and IGF-II was found and immunoblots did not reveal any alteration in the ratio of fragmented to intact IGFBP-3 during the menstrual cycle. A positive correlation between plasma levels of IGF-I and estradiol was seen in 8 out of 9 patients (P=0.012). Conclusions: The finding of a slight but significant higher level of plasma IGF-I in the follicular and luteal phases compared with the menstrual phase suggests plasma estradiol may influence the level of this growth factor. This hypothesis is further supported by the finding of a correlation between plasma levels of IGF-I and estradiol but not progesterone in individual patients at different times during the menstrual cycle.     

胰岛素样生长因子I与透明质酸对人关节软骨细胞的作用

目的探讨胰岛素样生长因子I(IGF-I)和透明质酸(HA)联合培养对人关节软骨细胞增殖及其生物学行为的影响.方法分离培养人关节软骨细胞,分4组,分别为对照组、IGF-I组、HA组和IGF-I+HA组.加入不同浓度的IGF-I、HA、IGF-I和HA,用四氮甲基唑蓝(MTT)法测定不同时间点软骨细胞增殖活性的变化.从第4代开始,用IGF-I和HA联合培养,通过电镜观察、甲苯胺蓝染色、Ⅱ型胶原和软骨蛋白聚糖(aggrecan)免疫组化及RT-PCR判断联合培养第8代软骨细胞表型的变化.自然传代的第6代细胞为对照组.结果 IGF-I在10μg/L浓度时即可明显促进软骨细胞的增殖,当IGF-I浓度为50μg/L时,其促增殖作用达最大值.单独应用不同浓度的HA对人关节软骨细胞的促增殖作用不明显.联合应用IGF-I与HA对软骨细胞的增殖具有协同效应并使促增殖作用时间后延.IGF-I和HA联合培养的第8代细胞胞质内含有丰富的粗面内质网和分泌小泡;RT-PCR显示Ⅱ型胶原mRNA表达阳性而Ⅰ型胶原mRNA表达阴性;甲苯胺蓝染色显示细胞质内有大量的紫色异染颗粒;Ⅱ型胶原和aggrecan免疫组化见92%的细胞染色呈阳性或强阳性,平均灰度分别为85.92±9.71和116.23±16.69.而对照组的平均灰度值分别为105.12±12.20和135.68±10.65,二者均显著低于对照组(P<0.01).结论 IGF-I明显促进软骨细胞的增殖;HA对软骨细胞的增殖无影响;二者联合培养促增殖能力更强,并且能有效地保持软骨细胞表型的稳定.     

胰岛素样生长因子在口腔黏膜下纤维性变组织中的表达

目的：探讨胰岛索样生长因子-1在口腔黏膜下纤维性变发病中的作用。方法：应用原位杂交的方法，对27例口腔黏膜下纤维性变（OSF）组织和9例正常组织进行了IGF-1mRNA的检测。结果：8例OSF早期患者角朊细胞中IGF-1mR-NA表达均为阳性，19例OSF中晚期组织有7例表达阳性，9例正常组织均为阴性，三组之间均有显著差异；所有组织中成纤维细胞IGF-1mRNA表达均为阳性，但强度无明显差异；中晚期组织有5例毛细血管内皮细胞表达阳性。结论：OSF病人角朊细胞可合成IGF-1，IGF-1可能在OSF发病中起重要作用。     

Genetic alterations in colorectal cancers with demethylation of insulin-like growth factor II

Loss of genomic imprinting is an epigenetic alteration of some cancers involving the absence of parental origin–specific expression of imprinted genes. Loss of genomic imprinting of insulin-like growth factor II is often detected in colorectal cancer. However, the genetic alterations accompanied by colorectal cancer with insulin-like growth factor II loss of genomic imprinting have not been fully determined. Genomic DNA samples were collected from 52 colorectal cancer tissues and analyzed. The loss of insulin-like growth factor II genomic imprinting status was determined by assessing the demethylation of the insulin-like growth factor II differentially methylated region using bisulfite sequencing. The molecular signatures were also examined: genetic mutations of KRAS, BRAF, and PIK3CA; the expression of CTNNB1 and TP53; and microsatellite instability status. Several cases of colorectal cancer with normal insulin-like growth factor II imprinting were located in the distal colon; in contrast, colorectal cancer with loss of genomic imprinting tended to be found in the proximal colon (22.7 versus 56.6%). The PIK3CA gene mutation was highly detected in normal imprinting tumors compared to colorectal cancers with insulin-like growth factor II loss of genomic imprinting (27.3% versus 6.7%). In multivariate analysis of these clinicopathologic and molecular factors of tumors, statistically significant relationships were observed among the proximal location of the tumor (odds ratio, 12.9; 95% confidence interval, 1.52-110.13), PIK3CA genetic mutation (odds ratio, 0.082; 95% confidence interval, 0.01-0.73), and insulin-like growth factor II genomic imprinting status. Our findings indicate that colorectal cancers with demethylation of the insulin-like growth factor II gene are distinct from normal imprinting tumors, both in clinical and genetic features.     

人胰岛素样生长因子-1的真核表达及其生物学功能研究

目的：构建人胰岛素样生长因子1（IGF-1）分泌型真核表达载体，并检测表达产物的生物活性。 方法：用RT-PCR法从人肝细胞克隆IGF-1基因，并将其连入Psec Tag/FRT/V5-His载体，用脂质体法转染CHO细胞，将转染细胞上清培养骨髓基质干细胞，用MTT法测定骨髓基质干细胞的增殖情况。 结果：成功扩增210 bp的IGF-1基因，表达产物经SDS-PAGE分析及Western blotting检测具有7.7 kD特异性条带。骨髓基质干细胞的增殖随转染细胞上清的浓度、转染细胞上清培养时间的增加而增加。 结论：成功构建分泌型IGF-1真核表达载体，其表达产物对骨髓基质干细胞具有促增殖作用。     

Testosterone, dehydroepiandrosterone, insulin-like growth factor 1, and insulin in sedentary and physically trained aged men

The influence of physical activity on dehydroepiandrosterone sulfate (DHEAS), total and free testosterone (TT and FT, respectively), insulin-like growth factor I (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and insulin concentrations in aging men was investigated. Eight trained and nine sedentary men aged 60–65 years volunteered to participate in this study. Physical activity was determined during an effort test and evaluated by the measure of the maximal aerobic power ( ). In the trained aging men, the was higher than in the sedentary group of matching age [mean (SD) 206.8 (17.1) W versus 136.6 (12.3) W; P<0.0001]. The fat percentage was higher in the sedentary (n=9) than in the trained (n=8) group [23.9 (3.2)% versus 14.6 (3.7)%; P<0.0001]. DHEAS and IGF-1 levels were higher in trained than in sedentary subjects, respectively 2.04 (1) μmol/l versus 1.01 (0.68) μmol/l (P=0.02) and 192.1 (40.1) ng/ml versus 132.8 (31.2) ng/ml (P=0.003). Insulin levels were higher in sedentary subjects [11.2 (3.5) mIU/l versus 7.6 (2.2) mIU/l, P=0.03]. No statistical difference was observed between both groups for FT and total TT values, FSH values and LH values. IGF-1 was correlated with (r=0.64, P=0.003), and DHEAS was correlated with IGF-1 (r=0.59, P=0.01). We observed a relationship between fat percentage and each of the following hormones: IGF-1 (r=–0.50, P=0.03), FT (r=–0.66, P=0.002), TT (r=–0.54, P=0.02) and insulin (r=0.63, P=0.004). Insulin was inversely correlated with FT (r=–0.66, P=0.002) and TT (r=–0.47, P=0.05). These results suggest that regular physical activity could maintain higher DHEAS and IGF-1 and lean body mass levels in elderly men, and participate in general well being in older age. Electronic Publication