胰岛素样生长因子与血细胞生成

本文对胰岛素样生长因子类（ＩＧＦｓ）、其特异性受体及结合蛋白在不同类型造血细胞中的作用做一综述，发现几乎所有的造血细胞，无论正常还是恶性的，均表达有ＩＧＦｓ受体，有些甚至还产生ＩＧＦｓ或其结合蛋白。ＩＧＦｓ参与正常的红细胞、粒细胞及淋巴细胞的生成，ＩＧＦｓ，特别是ＩＧＦ－Ｉ对白血病细胞具有促分裂原作用。某些不成熟细胞系的分化伴有ＩＧＦｓ受体数量及亲合力的下降。据此，有人认为，ＩＧＦｓ在正常及恶性造血细胞中可能起重要作用。     

胰岛素样生长因子与血细胞生成

本文对胰岛素样生长因子类（ＩＧＦｓ）、其特异性受体及结合蛋白在不同类型造血细胞中的作用做一综述。发现几乎所有的造血细胞，无论正还是恶性的，均表达有ＩＧＦｓ受体，有些甚至还产生ＩＧＦｓ或其结合蛋白。ＩＧＦｓ参与正常的红细胞、粒细胞及淋巴细胞的生成。ＩＧＦｓ、特别是ＩＧＦ－Ｉ对白血病细胞具有促分裂原作用，某些不成熟细胞系的分化伴有ＩＧＦｓ受体数量及亲合力的下降。据此，有人认为，ＩＧＦｓ在正常及恶性造血     

血清胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3在矮小症儿童诊断和疗效判断中的价值

目的探讨胰岛素样生长因子-1（IGF-1）及其结合蛋白-3（IGFBP-3）在矮小症儿童诊断及疗效判断中的价值。方法1．对124例青春发育前矮小症患儿用精氨酸激发试验和可乐定激发试验检测其血清生长激素（GH）水平，并根据患儿GH峰值分为生长激素缺乏组（GHD组，40例）、特发性矮小组（1SS组，84例）。选取20例健康儿童作为健康对照组。对所有儿童采用酶联免疫吸附法检测血清IGF—1和IGFBP-3。对GHD组、ISS组和健康对照组儿童血清IGF-1和IGFBP-3水平进行两两比较。2．对15例GHD和30例ISS患儿予国产重组人生长激素（rhGH）0．1IU／（kg·d）治疗6个月，于治疗前及治疗6个月分别测定其身高、体质量、骨龄及血清IGF-1、IGFBP-3，并进行治疗前后的对照。结果1．GHD组和ISS组患儿血清IGF-1和IGFBP-3水平明显低于健康对照组（Pa〈0．01），GHD组与ISS组患儿血清IGF-1和IGFBP-3水平比较均有显著差异（Pa〈0．01），GHD组患儿治疗前后血清IGF-1、IGFBP-3比较有显著差异（Pa〈0．01）；诊断GHD，IGF-1的特异性为67．8％，敏感性为75％；IGFBP-3的特异性为88％，敏感性为85％。2．rhGH治疗后身高增长速度明显加快，血清IGF-1、IGFBP-3水平显著升高；治疗前血清IGF-1与治疗6个月生长速度呈显著负相关（r=-0．78P〈0．01）；治疗6个月后IGF-1的变化与治疗后生长速度呈显著正相关（r=0．82P〈0．01）。结论IGF-1、IGFBP-3可用于儿童矮小症的诊断及疗效评价。     

牛初乳短链胰岛素样生长因子-1对多柔比星肾病大鼠胰岛素样生长因子-1的影响

目的研究牛初乳短链胰岛素样生长因子-1（BctIGF-1）对肾病大鼠胰岛素样生长因子-1（IGF-1）的影响,为治疗肾病综合征（NS）提供理论依据。方法将30只周龄相同、体质量相近的雌性SD大鼠随机分为对照组、肾病组、BctIGF-1治疗组;实验第6周末杀鼠,采用放射免疫法测定其血清与尿IGF-1水平,反转录酶-聚合酶链反应（RT-PCR）测定其肝、肾组织IGF-1 mRNA表达,采用考马斯亮蓝法测定24h尿蛋白排泄量。结果BctIGF-1治疗组24h尿蛋白及病理积分均低于肾病组（P〈0.05,0.01）;肾病大鼠血清IGF-1水平明显低于BctIGF-1治疗组（P〈0.05）,尿IGF-1排泄量明显高于BctIGF-1治疗组（P〈0.01）;各组大鼠肝组织IGF-1 mRNA表达差异无显著性;肾组织IGF-1mRNA表达由高至低依次为对照组、BctIGF-1治疗组、肾病组,BctIGF-1治疗与对照组比较差异无显著性,但BctIGF-1治疗与对照组IGF-1 mRNA表达均显著高于肾病组（P〈0.01,0.05）。结论BctIGF-1可有效降低肾病大鼠尿蛋白,减轻肾脏病理损伤,其机制可能是通过增加其血清游离IGF-1水平、促进肾局部IGF-1mRNA表达来实现。     

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。     

单纯性肥胖儿童血清胰岛素样生长因子-1水平的临床研究

目的探讨单纯性肥胖儿童是否存在胰岛素样生长因子-1(insulinlikegrowthfactor1,IGF1)水平的异常,为防治儿童单纯性肥胖开辟新的医学途径。方法检测并分析50例单纯性肥胖儿童、30例健康儿童血清胰岛素、IGF1水平及血压。结果与健康儿童比较,单纯性肥胖儿童血清胰岛素、收缩压、舒张压增高,差异有显著性(P<0.05)。肥胖的程度不同,血糖、胰岛素、IGF1水平亦不同。对照组、轻、中、重度肥胖组的血糖、胰岛素、IGF1水平差异有统计学意义(F=8.79～14.82,P均<0.05)。重度肥胖组儿童的血糖浓度高于对照组和轻度肥胖组(P<0.05),而IGF1水平低于其他三组;中、重度肥胖儿童血清胰岛素水平高于对照组及轻度肥胖组(P<0.05);单纯性肥胖儿童血压高于健康儿童(P<0.05),高胰岛素血症的肥胖儿童血压明显高于胰岛素正常的儿童(P<0.01)。高胰岛素血症肥胖儿童IGF1水平低于胰岛素正常的儿童(P<0.01)。结论单纯性肥胖儿童,尤其是重度肥胖儿童,存在高胰岛素血症、高血压、IGF1水平低下及高血糖;IGF1水平下降是单纯性肥胖儿童物质代谢紊乱的危险信号,是肥胖儿童未来心血管疾病、糖尿病等的又一危险因素。     

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。     

胰岛素样生长因子-1受体基因与特发性矮小相关性研究进展

生长激素-胰岛素样生长因子(GH-IGF)轴是调节儿童生长发育中最重要的神经内分泌轴.胰岛素样生长因子-1受体( IGF-1 R)是调节该轴的激素受体级联反应的效应分子,它的分子结构或功能异常,将影响靶基因IGF-1与其结合,从而引起生长障碍,可能与特发性矮小(ISS)发生有一定关系.国内外尚无IGF-1R基因与ISS的研究,为探讨其与ISS的关系,现就近年来有关IGF-1 R与人体生长障碍的研究作简要综述.     

胰岛素样生长因子-1受体基因变异与矮身材的研究进展

胰岛素样生长因子-1受体(IGF-1 R)是下丘脑-垂体-生长激素轴IGF信号通路的受体级联效应分子.近年来,国外IGF-1R基因突变矮身材报道逐年增多,现将IGF-1R基因缺陷与矮身材的研究进展总结如下,以期引起临床医师的重视.     

病毒性心肌炎小鼠不同时点胰岛素样生长因子-1及其相关蛋白的表达

目的探讨胰岛素样生长因子-1（IGF-1）及其相关蛋白在病毒性心肌炎病程中的作用。方法取Balb／C小鼠60只，随机分为病毒实验组40只，腹腔感染CVB3病毒，分别于实验d3、7、15、30采血、取心肌组织；空白对组（未感染CVB3病毒小鼠）20只。用酶联免疫吸附测定法（ELISA）检测其血浆IGF-1的表达，用免疫组织化学法和逆转录酶多聚链反应（RT-PCR）技术检测其心肌组织IGF-1及相关蛋白的表达。结果病毒性心肌炎小鼠血浆IGF-1及相关蛋白表达均较空白对照组高，且在感染病毒后表达渐增高，15d达最高峰，30d表达降低，但仍维持一较高水平，与对照组比较仍有显著差异（F=19．53 P〈0.05），其在心肌组织中的表达与血浆中的表达变化规律一致。结论IGF-1及其相关蛋白可能参与小鼠CVB3病毒性心肌炎的病理生理过程。     

Insulin-like growth factor-1 expression in reflux nephropathy

Background Reflux nephropathy (RN) is recognised as a major cause of end-stage renal failure in children and young adults. Insulin-like growth factor-1 (IGF-1), a peptide growth factor produced by collecting ducts, and its receptor, insulin-like growth factor-1 receptor (IGF-1R), are present in the glomeruli and basolateral membrane of renal proximal tubular cells. Exogenous IGF-1 has been shown to enhance proliferation and reduce apoptosis of tubular cells following renal injury.Methods We designed this study to investigate the expression of IGF-1 in RN. The kidney specimens from 15 children with RN were obtained at the time of nephrectomy. Control material included normal kidney specimens obtained from adult patients during partial nephrectomy for an incidentaloma. Single-label immunofluorescence histochemistry was carried out using polyclonal antibodies to IGF-1 and IGF-1R employing laser scanning confocal microscopy. Double-label immunofluorescence histochemistry was carried out using monoclonal antibodies to vimentin and clusterin to assess tubulointerstitial fibrosis. IGF-1 and IGF-1R gene expression were evaluated by in situ hybridisation (ISH). The TUNEL method was utilised to assess tubular apoptosis.Results In the normal kidney there was strong IGF-1 and IGF-1R immunoreactivity in the proximal tubules, whereas IGF-1 and IGF-1R immunoreactivity was markedly reduced in RN specimens. Strong IGF-1 and IGF-1R mRNA expression was observed in the proximal tubules in normal kidneys, whereas IGF-1 and IGF-1R mRNA expression was undetectable in RN. Renal tubulointerstitial expression of vimentin and clusterin was markedly increased in RN kidneys. Decreased IGF-1 and IGF-1R expression in RN strongly correlated with severity of tubular apoptosis in RN compared with controls.Conclusion These data suggest that the downregulation of IGF-1 and IGF-1R may play an important role in the pathogenesis of RN, at least in part by increasing interstitial collagen deposition and tubular apoptosis.     

The insulin-like growth factor I generation test in the investigation of short stature

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 ± 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 ± 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.     

Insulin-like growth factor-1 as an indicator of nutrition during treatment of adolescent girls with eating disorders

AIM: The use of serum insulin-like growth factor-1 (IGF-1) concentrations as an index of nutrition has been analysed in teenage girls with eating disorders and weight loss. METHOD: Blood samples for analysis of IGF-1 were obtained at 349 assessments of 302 patients and biweekly during 56 treatment periods in 46 patients. IGF-1 was related to body size, weight loss, degree of leanness (BMI standard deviation score) and rate of weight loss. RESULTS: At assessment, when most of the girls were on a weight-losing course, serum IGF-1 concentrations were low. Weight loss immediately prior to assessment was the most important predictor of IGF-1. Together with measurements of weight, height, weight loss and BMI standard deviation score the rate of weight loss predicted IGF-1 to 32-55%. During treatment when there was net weight gain, IGF-1 increased in parallel with the BMI standard deviation score, a measure of leanness, and was also influenced by the short-term weight trend. CONCLUSION: The serum IGF-1 concentration is an indicator of nutritional status in adolescents with eating disorders. It is sensitive to short-term weight changes measured in a clinical setting and could be used at assessment and to monitor nutritional rehabilitation.     

儿童身材矮小的病因分析及遗传学诊断

目的 探讨身材矮小患儿的病因分布及遗传学诊断。方法 回顾性分析86例身材矮小患儿的病因分布及临床特征。结果 86例身材矮小患儿中,病因有6种,以特发性矮小症（ISS,41%）和生长激素缺乏症（GHD,29%）最常见,遗传性疾病（14%）次之。将遗传性疾病组与ISS组、GHD组比较显示,各组患儿就诊年龄、身高、出生身长、出生体重、父母身高及胰岛素样生长因子1（IGF-1）水平差异均无统计学意义（P > 0.05）,但遗传性疾病组身高距同年龄同性别个体身高第3百分位数的差值（ΔP3）和身高标准差评分（HtSDS）显著低于ISS组（P < 0.05）,但与GHD组相比差异无统计学意义（P > 0.05）。对遗传性疾病组患儿的临床表现进行分析,显示不同遗传性疾病表型谱存在异质性及表型重叠性。结论 ISS、GHD和遗传性疾病是儿童身材矮小的主要病因。对存在严重身材矮小的患儿,在除外GHD外,有必要进一步行遗传学检查明确诊断。     

Etiological profile of short stature

Objective : To study the frequency of various causes of short stature and their etiological contribution in a referral endocrinology and metabolism clinic at a tertiary care hospital.Methods : 352 children with growth retardation attending endocrine clinic between Feb 1999 to Mar 2001 were investigated for etiology of short stature. Agrawal’s growth chart was used for percentiles and height velocity. Various relevant radiological, biochemical and hormonal investigations were performed.Results : Normal variant short stature was the most common cause of short stature followed by endocrine causes.Conclusion : In males most common cause of short stature was constitutional growth delay, while in females most common cause of short stature was familial short stature.     

人矮小同源盒基因在身材矮小中的研究进展

儿童身材矮小是儿科内分泌常见病,现已证实人矮小同源盒基因(SHOX基因)的缺失和突变是儿童Leri-Weill综合征、Turner综合征及特发性身材矮小和其他具有矮小表型疾病的分子遗传学基础,SHOX基因缺陷的临床表型具有明显的异质性,早期发现SHOX基因的缺陷对矮小症的诊断和治疗具有重要的参考价值和指导意义.     

身材矮小相关基因研究进展

人类身高主要受下丘脑-垂体-生长激素轴调控,也受营养和体育锻炼等其他因素的影响,其中遗传因素是影响身高个体差异的主要原因,遗传度约为80%。目前国内外对导致身材矮小的基因分析已有较大的收获,与身高有关的基因达180多种。现就一些主要相关基因作一综述,主要包括腺垂体发育缺陷相关基因、生长激素释放激素-生长激素-胰岛素样生长因子1轴相关基因突变,以及其他相关基因突变和表现。     

胰岛素样生长因子-1在新生儿高胆红素血症中的变化及意义

目的：胰岛素样生长因子-1(IGF-1)是神经系统必需的调节因子,目前少有报道其与高胆红素血症之间的关系。该文主要通过测定高胆红素血症（高胆）新生儿血清中IGF-1水平及新生儿神经行为评分(NBNA)来探讨IGF-1与高胆的关系及其临床意义。方法：应用电化学发光分析法检测57例高胆新生儿和 25例正常新生儿血清中IGF-1 浓度,同步测定血清总胆红素(TSB)、未结合胆红素(USB)及白蛋白(ALB)含量,计算USB与ALB比值(B/A),并行新生儿 NBNA 评分。高胆组按血清TSB值221~256 μmol/L,257~342 μmol/L,＞342 μmol/L分为轻、中、重三组;对照组TSB ＜85 μmol/L。结果：轻、中、重高胆患儿血清IGF-1浓度均值分别为39.38±8.42,30.77±4.65,26.34±2.05 ng/L,较对照组50.16±15.73 ng/ L明显降低,在轻、中、重高胆组间IGF-1浓度差异存在显著性(P＜0.01),其值随着胆红素的升高而降低;轻、中、重高胆组NBNA评分均值分别为35.01±2.26,32.45±2.74,26.77±5.02,明显低于对照组38.24±0.78(P＜0.01),高胆各组间差异也有显著性(P＜0.01);血清IGF-1 浓度与NBNA评分呈正相关(r=0.603, P＜0.01),与B/A值呈负相关(r=-0.483, P＜0.01)。结论：高胆患儿血清IGF-1浓度显著降低,降低程度与血清胆红素水平有关;IGF-1可能与新生儿胆红素脑损伤密切相关。［中国当代儿科杂志,2009,11（5）：357-360］     

血管内皮生长因子及胰岛素样生长因子-1在早产儿视网膜病变中的作用

早产儿视网膜病变(retinopathy of prematurity,ROP)多发生于早产儿尤其是极低出生体重儿,是导致儿童视力下降甚至失明的重要原因.视网膜新生血管形成是其主要的病理特点,血管内皮生长因子(vascular endothelial growth factor,VEGF)及胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)通过控制血管内皮细胞增殖,在新生血管形成中起到了关键作用.近年来临床研究表明,玻璃体内注射VEGF抑制剂及生后早期提高早产儿血清IGF-1水平是防治ROP的有效方法.该文以国内外相关研究为背景,综述VEGF及IGF-1在早产儿视网膜病变发病过程中的作用,以及针对其作用机制而采取的防治方法.