生长激素缺乏症患儿血清胰岛素样生长因子-1及其结合蛋白的变化

目的 研究血清胰岛素样生长因子1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)浓度与生长激素缺乏症(GHD)患儿生长激素(GH)激发试验中血清GH峰值关系,为其代替GH激发试验提供依据。方法选择GHD患儿62例(男39例,女23例),为GHD组;60例健康儿童(男38例,女22例)为对照组。分别用放射免疫分析法(RIA)、免疫放射分析法(IRMA)检测两组血清IGF-1、IGFBP-3浓度,同时做GH激发试验,测定血清GH峰值,并比较其与IGF-1、IGFBP-3的关系。结果 GHD血清IGF-1、IGFBP-3均显著低于对照组(t=3.116、11.579 P均<0.01);GHD组血清IGF-1、IGFBP-3浓度与GH激发试验中GH峰值呈显著正相关(r=0.331、0.347 P均<0.01);GHD组血清IGF-1、IGFBP-3降低阳性率分别为97.58％、98.38％,与激发试验的阳性率(100％)比较无统计学意义(x~2=3.074、2.033 P均>0.05)。结论 血清IGF-1、IGFBP-3浓度的检测对诊断GHD有重要意义;检测血清IGF-1、IGFBP-3浓度可替代GH激发试验。     

特发性矮小患儿生长激素-胰岛素样生长因子轴变化的研究

目的 观察特发性矮小(ISS)患儿血中生长激素(GH)、胰岛素样生长因子-l(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及生长激素结合蛋白(GHBP)水平的变化.方法 2002年6月至2006年5月在中南大学湘雅二医院儿科就诊的37例ISS患儿为病例组,37例年龄性别相匹配的正常儿童为对照组.采用放射免疫分析法(RIA)测定血清GH,免疫放射计量法(IRMA)测定血清IGF-1及IGFBP-3,葡聚糖覆盖炭末吸附法(DCT)检测血清GHBP.结果 ISS组血清GHBP、IGF-1、IGFBP-3均明显低于对照组(均P＜0.01),而血清GH基础值在ISS组明显高于时照组(P＜0.05).结论 ISS患儿血中IGF-1和IGFBP-3降低可能是其矮小的原因之一.ISS患儿血中反映生长激素受体(GHR)水平的GHBP降低,而GH基础值升高,提示可能存在因GHR缺陷导致的GH不敏感.     

矮小儿童下丘脑-垂体及其胰岛素样生长因子轴功能检查的意义

目的检测矮小儿童下丘脑-垂体及其胰岛素样生长因子(IGF-1)生长轴(GHRH-GH-IGF-1)功能,了解矮小儿童的发病因素及确定下丘脑-垂体及其IGF轴功能缺陷病因分类。方法矮小儿童30例。用统一印制的矮小儿童表格记录其临床特征。对矮小儿童进行甲状腺功能测定;用胰岛素 左旋多巴行生长激素(GH)刺激试验;放射免疫法测定血清IGF-1和血清胰岛素样生长因子结合蛋白-3(IGFBP-3)水平;同时行患儿骨龄、垂体增强MRI扫描、染色体核型分析、性激素测定。根据矮小症诊断标准和2004年Rosenfeld RG和GHRH-GH-IGF-1轴缺陷不同,将矮小儿童进行病因定位和分类。结果矮小儿童30例中,下丘脑-垂体及其IGF轴功能缺陷12例,占40%,其中肯定生长激素缺乏(GHD)4例,怀疑生长激素不敏感综合征2例,可疑GHD 6例。Turner′s综合征2例,占6.67%;体质性青春期延迟2例,占6.67%;特发性矮小14例,占46.6%。磁共振发现垂体微腺瘤2例;垂体发育不良12例。结论1.矮小儿童所占比例最大的为特发性矮小,其次为下丘脑-垂体及其IGF轴功能缺陷。2.IGF-1水平和IGFBP-3水平与生长激素刺激试验测定生长激素水平不一致,考虑存在生长激素抵抗和受体缺陷。3.矮小儿童可能存在先天性垂体发育异常,致使垂体分泌生长激素不足。     

短期生长激素治疗对营养不良矮小儿童血糖、甲状腺功能、胰岛素生长因子-Ⅰ、胰岛素生长因子结合蛋白-3的影响

目的探讨重组人生长激素(rhGH)短期治疗对营养不良矮小儿童空腹血糖(GLU)、甲状腺功能(TF)、胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合蛋白-3(IGFBP-3)的影响。方法选取16例年龄2～12岁、符合营养不良矮小诊断的患儿。采用rhGH治疗3个月。分别在治疗前、治疗1和3个月,取患儿清晨空腹血,测定GLU、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺素(TSH)、IGF-Ⅰ、IGFBP-3水平。采用方差分析比较3个时间点测量指标的均数。结果营养不良矮小儿童经rhGH治疗1和3个月后,GLU、T3、T4、TSH、IGFBP-3均无明显变化(Pa>0.05),IGF-Ⅰ明显高于治疗前,且有统计学意义(P<0.05)。结论rhGH短期治疗能使营养不良性矮小儿童的IGF-Ⅰ升高,且不影响GLU、TF。     

甲状腺功能减退症患儿血清生长激素、胰岛素样生长因子-Ⅰ、胰岛素样生长因子结合蛋白-3水平的变化

目的通过监测甲状腺功能减退症患儿生长激素(GH)、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)水平变化,探讨甲状腺功能减退症患儿GH-IGF轴与甲状腺素的变化规律。方法对56例甲状腺功能减退症(14例先天性甲状腺功能减退症和32例桥本病)患儿治疗前后血GH、IGF-Ⅰ、IGFBP-3水平和50例健康儿童血GH、IGF-Ⅰ、IGFBP-3水平进行监测。结果先天性甲状腺功能减退症新生儿9例患儿IGF-Ⅰ、IGFBP-3水平显著降低,经治疗后甲状腺功能逐渐恢复正常;5例先天性甲状腺功能减退症患儿和32例桥本病患儿无显著变化。结论先天性甲状腺功能减退症患儿存在GH-IGF轴功能紊乱,是导致身材矮小的重要原因,早期予甲状腺素治疗有利于维持患儿正常生长发育。     

先天性心脏病患儿营养不良与生长激素-胰岛素样生长因子轴的关系

目的探讨先天性心脏病（CHD）患儿营养不良与生长激素-胰岛素样生长因子（GH-IGF）轴的关系。方法依据有无发绀及心力衰竭,将50例CHD患儿分为发绀组13例、非发绀组37例;非发绀组又分为2个亚组：心力衰竭组25例、无心力衰竭组12例。20例健康儿童作为健康对照组,通过测定各组儿童血总蛋白、清蛋白及测量身高、体质量来评价其营养状况;采用免疫放射分析方法来检测血IGF-Ⅰ、胰岛素样生长因子结合蛋白-3（IGFBP-3）及生长激素结合蛋白（GHBP）,并进行比较。结果CHD患儿急、慢性营养不良的发生率分别为62%和28%,急性营养不良的发生率发绀组与非发绀组相似（P=0.105）;慢性营养不良的发生率发绀组高于非发绀组（P=0.006）;各组CHD患儿血清IGF-Ⅰ、IGFBP-3水平均下降,其中发绀组及心力衰竭组下降更为显著;发绀组及心力衰竭组患儿血GHBP水平下降。结论CHD患儿血清IGF-Ⅰ和IGFBP-3水平下降,考虑与生长激素受体（GHR）有关,GHR下调可能是GH抵抗或不敏感的分子机制之一,而GH抵抗或不敏感是CHD患儿发生急、慢性营养不良的原因之一。     

重组人生长激素治疗对特发性矮小症儿童血清Klotho和成纤维细胞生长因子23的影响北大核心CSCD

目的比较重组人生长激素(recombinant human growth hormone,rhGH)治疗前后特发性矮小症(idiopathic short stature,ISS)患儿血清Klotho、成纤维细胞生长因子23(fibroblast growth factor,FGF23)和胰岛素样生长因子(insulin-like growth factor,IGF)-1水平变化,探讨Klotho和FGF23与ISS患儿生长激素(growth hormone,GH)/IGF-1生长轴的关系。方法前瞻性选择2021年3月10日—2022年12月1日在河北省人民医院儿科确诊为ISS的33例儿童为ISS组,选择同期于儿童保健科就诊,年龄、性别与ISS组匹配的29例健康儿童为健康对照组。ISS组给予rhGH治疗,比较治疗前及治疗3、6、9个月血清Klotho、FGF23、IGF-1水平,并进行相关性分析。结果ISS组与健康对照组的血清IGF-1、Klotho、FGF23水平比较差异无统计学意义(P>0.05)。rhGH治疗3、6、9个月的ISS组血清Klotho、FGF23、IGF-1水平均较治疗前显著升高(均P<0.05)。ISS组治疗前Klotho、FGF23与磷酸盐水平均呈正相关(P<0.05);治疗前及治疗3、6、9个月的Klotho与IGF-1水平均呈正相关(P<0.05),FGF23与IGF-1水平均呈正相关(P<0.05),Klotho与FGF23水平均呈正相关(P<0.05),Klotho、FGF23水平与身高标准差积分无相关性(P>0.05)。结论rhGH治疗可上调Klotho、FGF23及IGF-1水平,实现ISS患儿的追赶生长。Klotho、FGF23可能并非直接促进ISS患儿线性生长,而是可能通过IGF-1及磷酸盐代谢等途径产生间接影响。Klotho、FGF23与IGF-1的一致变化表明三者在调节ISS线性生长中存在协同关系。     

孤独症谱系障碍儿童的血清胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3水平研究北大核心CSCD

目的探讨孤独症谱系障碍(autism spectrum disorder,ASD)儿童的血清胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)和胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)水平及与孤独症核心症状之间的关系。方法前瞻性选取重庆市妇幼保健院门诊招募的150名2~7岁ASD儿童和165名年龄、性别相匹配的正常健康儿童为研究对象,采用孤独症行为量表和孤独症评定量表评估ASD儿童核心症状,采用化学发光法检测两组儿童血清IGF-1和IGFBP-3水平。结果ASD组儿童血清IGF-1水平低于对照组儿童(P<0.05)。重度ASD儿童血清IGF-1和IGFBP-3水平低于轻-中度ASD儿童(P<0.001),2~3岁ASD儿童血清IGF-1水平低于对照组儿童(P<0.05)。两组男童IGF-1水平均低于女童(P<0.05)。血清IGF-1、IGFBP-3水平与儿童孤独症评定量表总分呈负相关(分别r=-0.32、-0.40,均P<0.001)。结论儿童早期血清IGF-1降低可能与ASD疾病发展相关,血清IGF-1和IGFBP-3水平与ASD儿童核心症状具有一定关联。     

胰岛素样生长因子-1在病毒性心肌炎小鼠中的变化及对心肌的保护作用

目的 探讨病毒性心肌炎（VMC）小鼠血清胰岛素样生长因子-1（IGF-1）水平的变化及外源性IGF-1对凋亡相关蛋白Bcl-2和Bax表达的影响。方法 Balb／c雄性小鼠随机分为3组：正常对照组、柯萨奇B3病毒（CVB3）感染组（感染组）和病毒感染加IGF-1治疗组。分别在实验d7、d14处死动物，留取血清、心肌标本。放射免疫法检测血清IGF-1水平，免疫组织化学法检测心肌组织Bcl-2和Bax蛋白表达。结果 感染组血清IGF-1水平较对照组明显降低，Bcl-2表达减少、Bax表达增加（P〈0．01）；治疗组较感染组Bcl-2表达增加、Bax表达减少（P〈0．01）。结论 IGF-1对VM小鼠的心肌细胞有保护作用。     

窒息新生儿血中胰岛素样生长因子-1和表皮生长因子水平的变化及其临床意义

目的观察窒息新生儿血中胰岛素样生长因子（IGF）-1、表皮生长因子（EGF）的动态变化，探讨窒息对新生儿胃肠功能影响的可能机制。方法用放射免疫分析法动态测定48例窒息新生儿和30例正常足月新生儿出生后1、3、7d血中IGF-1、EGF的水平变化。观察窒息新生儿胃肠功能障碍的发生情况。结果轻、重度窒息组从生后第1天IGF-1水平较对照组明显降低，差异有非常显著性（P〈0．01）；第7天轻度窒息组IGF-1恢复至对照组水平（B〉0．05），重度窒息组IGF-1仍较对照组低，差异有非常显著性（P〈0．01）。轻度窒息组生后第3天EGF水平较对照组明显降低；重度窒息组在生后第1天EGF水平较对照组明显降低，差异有非常显著性（P〈0．01）；第7天轻、重度窒息组EGF水平恢复至对照组水平（P〉0．05）。轻度窒息组有8例发生轻度胃肠功能障碍，重度窒息组有6例发生轻度胃肠功能障碍，3例发生中度胃肠功能障碍。3例发生重度胃肠功能障碍。结论窒息新生儿血中IGF-1、EGF水平的下降，可能是造成胃肠功能障碍的因素之一。     

Insulin-Like Growth Factor II Effects Mediated through Insulin-Like Growth Factor II Receptors

ABSTRACT. Insulin-like growth factor II (IGF-II) resembles the homologous peptide insulin-like growth factor I (IGF-I) in that it stimulates cellular growth in vitro. This effect is generally believed to be mediated through IGF type 1 receptors; the role of the IGF type 2 receptor remains, as yet, unknown. IGF-II has been shown to stimulate clonal expansion in cells from the human erythroleukaemia cell line K562, which displays binding of IGF-II and insulin but not IGF-I. This IGF-II effect was dose-dependent and correlated to the amount of specific binding; IGF-I did not stimulate growth. A similar effect on clonal growth was observed in the human T-cell line Jurkat. Furthermore, IGF-II was found to stimulate the cytotoxic activity of natural killer cells (as does interleukin 2). This effect was not inhibited by addition of IGF binding protein 1. Thus, it can be concluded that IGF-II, besides demonstrating standard IGF properties, exhibits unique biological effects in certain cells.     

Effects of Insulin-Like Growth Factor I in Man

ABSTRACT. A 6-day period of subcutaneous infusion with recombinant human insulin-like growth factor I in three healthy male volunteers resulted in an increase in the ratio of insulin to C-peptide levels and significant decreases in triglyceride levels and the ratio of total to high density lipoprotein—cholesterol in serum. Increased renal plasma flow and glomerular filtration rates were also observed.     

Secretion of a Large Molecular-Weight Form of Insulin-Like Growth Factor by a Primary Renal Tumor

A 5-year-old boy with an abdominal mass was found to have a primary renal tumor of poorly identifiable histology. Prior to resection of the tumor, the patient exhibited several episodes of biochemical hypoglycemia. The hypoglycemia did not recur after operation. Analysis of tumor tissue and of pre- and post-operative sera by column chromatography showed elevated insulin-like growth factor II (IGF-II) levels in the tumor; an abnormal large-molecular weight precursor form of IGF-II (pro-IGF-II) comprised 53% of total IGF-II in the tumor and 42% in preoperative serum. No pro-IGF-II was found in the serum 6 weeks post-operatively. Abnormal IGF-II secreted by the tumor may have mediated the hypoglycemia seen prior to tumor resection. This pediatric renal tumor is the first to our knowledge for which an association of non-islet cell tumor-related hypoglycemia and elevated tumor IGF-II content has been described. © 1995 Wi1ey-Liss, Inc.     

Comparative Immunohistochemical Study of Insulin-like Growth Factor II and Insulin-like Growth Factor ReceptorType 1 in Pediatric Brain Tumors

Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as “ependymoma”), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma. Received June 23, 1999; accepted September 30, 1999.     

Anabolic and Tissue Repair Functions of Recombinant Insulin-Like Growth Factor I

ABSTRACT. Recombinant human insulin-like growth factor I (rhIGF-I) has been produced in yeast and purified using conventional biochemical techniques. It has been shown to have receptor-binding properties and in vitro growth-promoting activities comparable to those of plasma-derived IGF-I. The anabolic actions of IGF-I can be studied using both systemic and local administration in vivo. The growth-promoting activity and systemic anabolic actions of recombinant IGF-I were studied in mutant dwarf rats. IGF-I was infused intravenously for 9 days and resulted in a significant gain in body weight and significant bone growth, though the effects were not as great as those observed with human growth hormone (hGH). IGF-I also had selective effects on specific organs which were not observed in hGH-treated animals. The results indicate that the growth-promoting effects of IGF-I show a different pattern compared to hGH. The effects of local administration of recombinant IGF-I on tissue regeneration and maintenance were also studied in hypophysectomized and normal rats. After hypophysectomy, the regeneration processes were impaired when both peripheral nerve regeneration and incision wound healing were considered. The results indicate that local administration could have significant effects on regeneration of, for example, peripheral nerves.     

生长激素缺乏儿童血清胰岛素样生长因子-1和瘦素水平的变化及其相互关系

目的探讨生长激素缺乏(GHD)儿童血清胰岛素样生长因子1(IGF1)、瘦素水平的变化。方法用放射免疫法分别检测20例正常青春期前儿童和23例GHD患儿血清IGF1和瘦素的水平。结果GHD组血清IGF1水平(51.158±29.988)μg/L低于对照组(112.680±41.540)μg/L,两者有显著差异(t=5.619P<0.01);瘦素水平(6.002±2.204)μg/L高于对照组(4.523±2.204)μg/L,两者比较有显著差异(t=2.225P<0.05);但IGF1和瘦素之间无相关性(P>0.05)。结论IGF1和瘦素对GHD患儿生长发育的调节作用是相互独立的。     

Insulin-Like Growth Factors (IGFs) and IGF Binding Proteins in Chronic Renal Failure: Evidence for Reduced Secretion of IGFs

To test the hypothesis that growth hormone (GH) insensitivity is responsible, amongst other mechanisms, for impaired growth in uraemic children, insulin-like growth factor I (IGF-I), IGF-II, IGF binding protein-1 (1GFBP-1), IGFBP-2 and IGFBP-3 were measured by radioimmunoassay in normal control children, in patients with end-stage renal failure (n = 51) and in patients with preterminal chronic renal failure (n = 11) and the production rate of IGF was calculated. A unique pattern of normal IGF-I and IGF-II levels and markedly increased levels of all three IGFBPs was present in uraemia. Measurement of free IGF-II binding capacity, and affinity cross-linking experiments showed that the excess immuno-reactive IGFBP was able to bind IGFs. To explain the excess of unoccupied IGF binding sites in uraemia, a mathematical model was developed which describes the production of IGFs and their interaction with IGFBP. Calculations of IGF secretion rates suggested that production of IGF is two orders of magnitude lower in uraemic children than in control children, despite normal GH secretion. It is concluded that in uraemia there is a relative GH insensitivity with respect to IGF production.     

人胰岛素样生长因子1基因质粒载体的构建及其在人脐血源性神经干细胞中的表达

目的 构建人胰岛素样生长因子1(IGF-1)质粒表达载体,并观察重组体pcDNA3.1-IGF-1转染后的脐血源性神经干细胞(NSCs)中IGF-1基因的表达情况.方法 通过反转录-PCR(RT-PCR)方法从胎肝中提取IGF-1基因,胶回收方法分别纯化PCR产物(IGF-1基因)和质粒pcDNA3.1,二者分别由DNA限制性内切酶BamH Ⅰ与 Hind Ⅲ双酶切后,经T4 DNA Ligase连接的方法将IGF-1基因克隆到质粒表达载体pcDNA3.1中,采用测序方法及DNA限制性内切酶BamH Ⅰ与 Hind Ⅲ双酶切方法鉴定重组质粒,脂质体转染法将重组体pcDNA3.1-IGF-1及空质粒pcDNA3.1分别转染至脐血源性NSCs内,经G418抗性筛选后,利用免疫细胞化学法和RT-PCR法检测IGF-1基因在基因转染脐血源性NSCs内的表达情况.结果 IGF-1基因从胎肝中成功提取.重组体pcDNA3.1-IGF-1经基因测序及DNA限制性内切酶BamH Ⅰ与 Hind Ⅲ双酶切证实质粒表达载体pcDNA3.1-IGF-1构建正确.重组体经脂质体法转染脐血源性NSCs 24 h后,经G418筛选2周得到细胞抗性克隆,免疫细胞化学法检测到IGF-1基因在重组质粒表达载体pcDNA3.1-IGF-1转染的脐血源性NSCs中成功表达.RT-PCR方法检测到重组质粒pcDNA3.1-IGF-1转染的脐血源性NSCs中IGF-1 mRNA表达阳性,而空质粒pcDNA3.1转染的脐血源性NSCs中IGF-1 mRNA表达阴性.结论 IGF-1基因可在重组质粒表达载体pcDNA3.1-IGF-1转染的脐血源性NSCs内成功表达.     

Serum Levels of Free Insulin-Like Growth Factor (IGF)-I in Normal Children

Serum levels of free insulin-like growth factor (IGF)-I were measured by immunoradiometric assay (IRMA) in fasting sera of 137 normal boys and 120 normal girls aged from 8 to 15 yr to study relationships between free IGF-I levels and ages, total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit (ALS) levels. In both sexes, serum free IGF-I levels and the ratios of free IGF-I to total IGF-I were significantly higher in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-I showed a significant positive correlation with those of total IGF-I, IGFBP-3 and ALS, while they showed a significant negative correlation with those of IGFBP-1. These observations suggest that increase in serum free IGF-I levels during puberty is caused by a dramatic increase in total IGF-I, rather than IGFBP-3, and a decrease in IGFBP-1. Also, high free IGF-I levels may play an important role in pubertal growth spurt.