胰岛素样生长因子与新生儿肺发育及肺损伤关系的研究进展

因肺发育和肺损伤过程复杂 ,涉及解剖、生理和细胞生物学 ,故至今尚无确切机制解释。近来发现胰岛素样生长因子 (insulin likegrowthfactor ,IGF)系统与肺发育及肺损伤有关 ,并通过基因调控、药物干预等方法调节IGF系统的产生及代谢 ,旨在促进肺发育 ,减轻肺损伤。本文就近年来的研究进展作一综述。1　IGF系统的组成和功能IGF系统由两种多肽 (IGF Ⅰ、 Ⅱ ) ,Ⅰ型和Ⅱ型IGF受体 (IGF ⅠR、 ⅡR) ,6种IGF结合蛋白 (IGFBP 1～ 6 )和它们的相应蛋白酶组成。IGF Ⅰ和Ⅱ是一类既有胰岛素样合成代谢作用 ,又有促生长作用的多肽 ,它…     

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。     

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目的探讨中枢神经系统感染患儿脑脊液中胰岛素样生长因子(IGFs)的变化及意义。方法选择2001年2月至2003年6月在新乡医学院一附院治疗的化脓性脑膜炎患儿30例、病毒性脑炎30例,以非中枢神经系统疾病、非感染性疾病的患儿30例作对照组。脑脊液中胰岛素样生长因子Ⅰ(IGFⅠ)用放射免疫分析法检测,脑脊液中胰岛素样生长因子Ⅱ(IGFⅡ)用免疫放射分析法检测。结果(1)化脓性脑膜炎患儿脑脊液中IGFⅠ、IGFⅡ质量浓度均显著高于病毒性脑炎组及对照组(P<0.01);(2)化脓性脑膜炎患儿脑脊液中IGFⅡ的质量浓度与蛋白质浓度呈正相关(r=0.821,P<0.05),与葡萄糖浓度呈负相关(r=-0.742,P<0.01);(3)化脓性脑膜炎患儿脑脊液中IGFⅠ的质量浓度与蛋白质浓度呈正相关(r=0.862,P<0.01)。结论IGFs参与了化脓性脑膜炎的病理生理过程,并参与了脑脊液中葡萄糖和蛋白质的代谢。脑脊液中IGFⅠ、IGFⅡ的浓度可作为鉴别化脓性脑膜炎和病毒性脑炎的一项辅助指标。     

1型糖尿病儿童血胰岛素样生长因子的变化

目的 探讨中国1型糖尿病病儿血胰岛素样生长因子－1（IGF－1）和胰岛素样生长因子结合蛋白－3（IGFBP－3）的变化。方法 糖尿病组46例,测定胰岛素治疗前、后血IGF－1、IGFBP－3等指标。对照组为正常儿童78例,测定空腹血IGF－1,IGFBP－3。结果 1．糖尿病组胰岛素治疗前血IGF－1和IGFBP－3均低于正常对照组,P＜0．01。经过胰岛素治疗,血IGF－1和IGFBP－3的水平随血糖水平的下降和C－肽水平的升高明显上升,仍低于对照组,P＜0．05。2．糖尿病组使用胰岛素治疗前血IGF－1和IGFBP－3分别与治疗前血糖浓度呈高度负相关关系,P＜0．05。胰岛素治疗前、后血IGF－1与血C－肽水平呈高度正相关关系,P＜0．05。结论 1型糖尿病病儿血IGF－1和TGFBP－3明显下降,青春期前血胰岛素和C－肽可能对IGF－1和IGFBP－3起主要调节作用。     

性早熟儿童甲状腺激素水平及与其他内分泌激素的关系

目的　了解性早熟儿童甲状腺轴激素水平及与其他内分泌激素水平的关系。方法　对 2 8例真性性早熟儿童及正常对照组 14例进行血清促甲状腺激素 (TSH)、T3 、T4、卵泡刺激素 (FSH)、黄体生成素 (LH)、雌二醇 (E2 )、胰岛素样生长因子 1(IGF 1)、胰岛素样生长因子结合蛋白 3(IGFBP3)、骨钙素 (BGP)等水平测定 ,对两组进行独立样本t检验 ,对观察组各指标进行两两指标相关分析。结果　TSH、T3 水平性早熟组高于对照组 ,但无统计学意义 (tT3=1.896 ,tTSH=0 .0 71　P均 >0 .0 5 ) ;T4水平低于对照组 ,但无统计学意义 (t=- 1.0 73　P >0 .0 5 )。T3 与IGF 1呈负相关 (r=- 0 .4 71　P <0 .0 5 ) ;TSH与IGFBP3呈正相关 (r =0 .4 5 8　P <0 .0 5 ) ;TSH与BGP呈负相关 (r =- 0 .4 91　P <0 .0 1) ;TSH、T3 、T4分别与FSH、LH、E2 值无相关关系 (P均 >0 .0 5 )。结论　性腺轴与甲状腺轴相对独立 ;甲状腺轴的促生长作用可能通过直接或间接方式调节IGF 1、IGFBP3分泌 ,甲状腺轴参与BGP的调节 ,促进骨骼生长     

血清胰岛素浓度的变化与肥胖儿童生长关系的探讨

目的探讨单纯性肥胖儿童的生长与其血清胰岛素(Ins)、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)浓度的关系。 方法2004 03中山大学附属二院对31例单纯性肥胖儿童及48例同龄正常儿童的生长参数及空腹Ins、IGF 1、IGFBP 3浓度进行测定,并进行比较及相关性分析。 结果肥胖组血清Ins、IGFBP 3浓度显著高于对照组(P<005,P<001),而两组间IGF 1差异则无显著性意义,血清Ins浓度与BMI、IGFBP 3呈正相关,肥胖儿童身高SDS与1NS、IGF 1正相关。 结论肥胖儿童存在有非生长激素(GH)依赖性生长的代偿机制。其中高胰岛素血症可能参与了这一过程,它既可以通过增加IGFBP 3的合成来间接提高IGF 1的生物活性,又可以直接发挥促生长作用。     

胰岛素样生长因子结合蛋白7与肿瘤

胰岛素样生长因子结合蛋白7(insulin-like growth factor binding protein 7,IGFBP7)通过与胰岛素样生长因子(insulin-like growth factor,IGF)、胰岛素相结合,延长IGF/胰岛素的半衰期,从而发挥IGF/胰岛素的生物学功能.与其他结合蛋白不同的是,IGFBP7能与胰岛素强有力的结合,从而能够不依赖IGF而发挥功能.IGFBP7在细胞生长、增殖和在肿瘤细胞的黏附、浸润、迁徙及肿瘤血管的形成等方面发挥作用,可能与某种信号传导通路有关.     

IGF轴与胎儿生长调节

胰岛素样生长因子 (IGFs)及其受体、结合蛋白、结合蛋白酶构成IGF轴 ,在胎儿生长调节中起关键作用 ;IGF转基因动物生长加速 ,IGF基因敲除动物宫内生长迟缓 ;宫内生长发育迟缓小样儿IGF轴异常 ,重组IGF Ⅰ对其有治疗作用。     

胰岛素样生长因子-1(IGF-1)对缺氧缺血脑损伤新生鼠内源性IGF-1和IGF-1受体基因表达的影响

目的　胰岛素样生长因子 1(IGF 1)对损伤的神经组织有修复作用 ,但外源性IGF 1是否会抑制内源性IGF 1、IGF 1受体的生成 ,从而减弱IGF 1的神经保护作用尚不明确。本文通过观察IGF 1治疗新生大鼠缺血缺氧脑损伤 (HIBD)后脑IGF 1和IGF 1受体mRNA水平的变化 ,研究IGF 1对HIBD新生大鼠内源性IGF 1、IGF 1受体的影响。方法　制作新生大鼠HIBD模型 ,用原位杂交方法观察HIBD后各时间点海马和大脑皮层IGF 1和IGF 1受体基因表达的动态变化 ,并比较IGF 1治疗组与未治疗组HIBD后 12h、72hIGF 1、IGF 1受体mRNA的表达水平。结果　HIBD后 4 8h海马IGF 1和IGF 1受体mRNA开始升高 ,72h达高峰。损伤后 12 0h ,IGF 1mRNA降至正常水平 ,而IGF 1受体mRNA仍处于较高水平。在皮层 ,IGF 1和IGF 1受体mRNA开始升高时间稍早于海马 ,2 4h上升 ,96h降至正常 ,但是上升幅度相对较小。与未治疗组比较 ,IGF 1治疗后内源性IGF 1表达无明显变化。IGF 1受体的表达在治疗后 12h无明显差别 ,但在 72h时显著增加。结论　HIBD后皮层、海马等脑损伤区的IGF 1和IGF 1受体表达均升高。给予外源性IGF 1后并不降低内源性IGF 1的表达 ,还能刺激IGF 1受体表达增加。     

胰岛素样生长因子-1(IGF-1)对缺氧缺血脑损伤新生鼠内源性IGF-1和IGF-1受体基因表达的影响

目的　胰岛素样生长因子 1(IGF 1)对损伤的神经组织有修复作用 ,但外源性IGF 1是否会抑制内源性IGF 1、IGF 1受体的生成 ,从而减弱IGF 1的神经保护作用尚不明确。本文通过观察IGF 1治疗新生大鼠缺血缺氧脑损伤 (HIBD)后脑IGF 1和IGF 1受体mRNA水平的变化 ,研究IGF 1对HIBD新生大鼠内源性IGF 1、IGF 1受体的影响。方法　制作新生大鼠HIBD模型 ,用原位杂交方法观察HIBD后各时间点海马和大脑皮层IGF 1和IGF 1受体基因表达的动态变化 ,并比较IGF 1治疗组与未治疗组HIBD后 12h、72hIGF 1、IGF 1受体mRNA的表达水平。结果　HIBD后 4 8h海马IGF 1和IGF 1受体mRNA开始升高 ,72h达高峰。损伤后 12 0h ,IGF 1mRNA降至正常水平 ,而IGF 1受体mRNA仍处于较高水平。在皮层 ,IGF 1和IGF 1受体mRNA开始升高时间稍早于海马 ,2 4h上升 ,96h降至正常 ,但是上升幅度相对较小。与未治疗组比较 ,IGF 1治疗后内源性IGF 1表达无明显变化。IGF 1受体的表达在治疗后 12h无明显差别 ,但在 72h时显著增加。结论　HIBD后皮层、海马等脑损伤区的IGF 1和IGF 1受体表达均升高。给予外源性IGF 1后并不降低内源性IGF 1的表达 ,还能刺激IGF 1受体表达增加。     

Growth impairment, IGF I hyposecretion and thyroid dysfunction in children with perinatal HIV-1 infection

We evaluated the growth pattern, bone age, insulin-like growth factor I (IGF I) secretion and thyroid function in 24 perinatally infected children: 9 asymptomatic or paucisymptomatic (group 1) and 15 with a more advanced disease state and treated with zidovudine (group 2). Statural and ponderal growth were compared with those of 37 at-risk children who seroreverted. During the two-year follow-up, 22% of children in group 1 had impaired growth, 33% bone age delay, 45% reduced IGF I levels but none had thyroid dysfunction. In group 2, 53% had growth failure, 53% bone age delay, 86% reduced JGF I levels and 40% thyroid dysfunction. Among seroreverters, none showed growth impairment; statistically significant differences were found for height, weight and height velocity between perinatally infected children and seroreverters. Since auxological and hormonal evaluations run parallel to the clinical course of infection, these indices may be useful in monitoring disease progression.     

三种不同类型性早熟女童骨生长及骨代谢变化研究

目的探讨真性特发性性早熟女童三种不同类型胰岛素样生长因子1（IGF1）、骨龄（BA）及骨密度（BD）的变化。方法真性特发性性早熟女童196例,分为快速进展型、缓慢变化型及生长相对迟缓型,分别检测不同类型性早熟女童IGF1、BA及BD,并进行三种类型间比较,观察其骨生长及骨代谢的变化。结果快速进展型性早熟女童其IGF1、BA显著高于缓慢变化型及生长相对迟缓型女童（P〈0．05）;缓慢变化型女童IGF1及BA高于生长相对迟缓型患儿（P〈0．05）,生长相对迟缓型患儿其IGF1明显降低,甚至低于同年龄女童正常值,BA与实际年龄相当,BD在三种类型患儿间差异无统计学意义。结论快速进展型女童存在明显的骨生长加速、成熟提前,生长潜力缩短;缓慢变化型女童尽管也存在骨生长、成熟加速,但生长速度、骨成熟进程相对较缓;生长相对迟缓型女童骨生长迟滞,呈现出性腺轴与生长轴分离现象。     

IGF, IGF receptor and overgrowth syndromes

The insulin-like growth factors are a family of growth factors, binding proteins and receptors that are involved in normal growth as well as in a number of pathological states. Overgrowth syndromes are a group of disorders characterized by a phenotype of excessive somatic and visceral growth. In addition, patients suffering from overgrowth syndromes are predisposed to develop cancer. Several specific defects linked to the insulin-like growth factor system were elucidated for a group of these disorders, including Simpson-Golabi-Behmel syndrome, Bannayan-Ruvalcaba-Riley syndrome and Beckwith-Wiedemann syndrome. The aim of this review is to examine recent data linking the phenotype of overgrowth syndromes, visceral growth and increased risk of neoplasia, with the molecular machinery of the IGF system.     

Structural alteration of the insulin-like growth factor II-gene in Wilms tumour

In this study messenger ribonucleic acid (mRNA) and DNA of five Wilms tumours were investigated. As expected, the level of insulin-like growth factor (IGF) II-mRNA was elevated up to 50 times in tumour tissue as compared to normal adjacent kidney tissue. In addition, genomic DNA was isolated and digested with appropriate restriction enzymes. Southern blots were prepared and hybridized to IGF II-cDNA probes. Additional bands were present in one of the five Wilms tumours compared to normal tissue. The results indicate a rearrangement of the IGF II-gene on one of the two chromosomes. It is speculated, that this change is responsible for the elevated IGF II expression which may be a factor contributing to tumour growth.Abbreviations cDNA complementary deoxyribonucleic acid - IGF insulin-like growth factor - mRNA messenger ribonucleic acid     

Placental IGF-I, IGFBP-1, zinc, and iron, and maternal and infant anthropometry at birth

Aim: To correlate placental protein levels of insulin‐like growth factor (IGF)‐I and insulin‐like growth factor binding protein (IGFBP)‐1, with previously determined levels of IGF‐I and IGF‐II mRNA expression, and the micronutrients zinc and iron, and maternal and newborn anthropometry. Methods: Placental samples were collected from rural field sites in Pakistan. Samples were divided into small and large for gestational age groups (SGA and LGA, respectively). IGFBP‐1 levels were assessed using Western immunoblotting. IGF‐I protein levels were assessed using ELISA techniques. IGF mRNA expression, zinc, and iron, were quantified as previously described and were used for comparative purposes only. Results: Thirty‐three subjects were included (SGA, n = 12; LGA n = 21). Higher levels of IGFBP‐1 were seen in the SGA group (p < 0.01). IGFBP‐1 correlated positively with maternal and infant triceps skin‐fold thickness in the LGA and SGA groups, respectively (p < 0.05). Significantly lower IGF‐I protein levels were seen in the SGA group. IGF‐I levels correlated significantly with maternal and newborn anthropometry. IGFBP‐1 correlated significantly with IGF‐II mRNA expression (p < 0.05). Conclusion: Placental protein levels of IGF‐I and IGFBP‐1 appear to be associated with maternal anthropometry. Maternal anthropometry may thus influence IGFBP‐1 and IGF‐I levels and may possibly be used for screening of pregnancies, with the potential for timely identification of these high‐risk pregnancies.     

不同胎龄儿脐血IGF-1、IGFBP-1及CP水平的变化

目的 了解胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)及C肽(CP)对不同胎龄新生儿出生体重的影响。方法 选取不同胎龄的新生儿共76例,按孕周分为≤32、-34、-36、-38、-40、-42周6组,均为适于胎龄儿。分娩时取脐静脉血3 ml,用EIASA法测定血清IGF-1、IGFBP-1及CP。结果 自32周至40周,血清IGF-1、CP逐渐增加,IGFBP-1逐渐下降,各组间差异有显著意义(除34与36周三者比较P>0.05外),但至42周时,IGF-1、CP开始下降,IGFBP-1上升,与40周相比,P<0.05。IGF-1、CP均与胎龄呈中度正相关,而IGFBP-1与胎龄呈高度负相关。结论IGF-1、CP能促进孕晚期胎儿宫内生长,而IGFBP-1则对胎儿生长起抑制作用。因此,营养物质-胰岛素-胰岛素样生长因子系统代谢轴是孕后期调节胎儿生长的重要系统。     

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.     

Impact of intrauterine growth retardation and early protein intake on growth, adipose tissue, and the insulin-like growth factor system in piglets

Small birth weight and excess of early protein intake are suspected to enhance later adiposity. The present study was undertaken to determine the impact of diets differing in protein content on short-term growth, adipose tissue development, and the insulin-like growth factor (IGF) system in piglets. Normal (NW) and small (SW) birth weight piglets were fed milk-replacers formulated to provide an adequate (AP) or a high protein (HP) supply between 7 and 28 d of age. The fractional growth rate was higher (p < 0.01) in SW than in NW piglets. At 7 d of age, the lower (p < 0.05) weight of perirenal adipose tissue relative to body mass in SW than in NW piglets did not involve significant changes in plasma IGF-I, leptin, or insulin-like growth factor binding protein levels, but involved differences (p < 0.05) in the expression of IGF-I and leptin in adipose tissue. Growth rates did not differ between AP and HP piglets. At 28 d of age, HP piglets had lower (p < 0.001) relative perirenal adipose tissue weight but did not differ clearly from AP piglets with regard to the IGF system. It remains to be determined whether piglets fed such a high protein intake will stay subsequently with a low adiposity.     

Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth

AIM: Normal variation in size at birth is a result of the interaction between fetal genetic factors and the maternal uterine environment. It is, however, unclear how genetic factors contribute to fetal growth. The insulin-like growth factor (IGF) system regulates uterine, placental and fetal development, thereby partially controlling the rate of fetal growth. The aim of this study was to investigate the associations between the neonatal birth weight and the genotypes of polymorphic loci in the IGF2 and IGF2 receptor (IGF2R) genes. METHODS: We determined the genotypes of two polymorphic loci in the IGF2 gene and four loci in the IGF2R gene in 884 pairs of normal Japanese mothers and their neonates, and compared the genotypes with the birth weight converted into standard deviation scores (SDSs) according to sex, parity and gestational weeks at delivery. RESULTS: There was a significant difference in birth weight SDSs among the three neonatal +3123/ApaI genotypes of the IGF2 gene; AA, AG and GG. There was also a significant difference in birth weight among the three neonatal c.901C > G genotypes of the IGF2R gene; CC, CG and GG. Conclusion: These findings indicate that both IGF2 and IGF2R gene variants are associated with fetal growth.