胰岛素样生长因子及胰岛素样生长因子结合蛋白-3与胎儿生长受限的关系

目的　探讨胰岛素样生长因子 (IGF) Ⅰ、IGF Ⅱ和IGF结合蛋白 3(IGFBP 3)与胎儿生长的关系 ,以及IGF在胎儿生长受限 (FGR)发病中的作用。方法　选取 2 0例分娩FGR胎儿 (FGR组 )、10例分娩巨大儿 (巨大儿组 )及 2 0例分娩正常儿 (对照组 )的产妇 ,抽取 3组产妇分娩后肘静脉血及其新生儿脐静脉血 ,分离血清。采用放射免疫法和免疫放射法测定 3组产妇及其新生儿血清中IGF Ⅰ、IGF Ⅱ及IGFBP 3的水平。结果　 (1)FGR组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为(130 5± 2 6 0 ) μg/L、(2 40± 0 42 ) μg/L及(5 5 79± 848) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 6± 1 7) μg/L、(1 5 4± 0 31) μg/L及 (86 9± 183) μg/L。 (2 )巨大儿组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 9 7± 44 6 ) μg/L、(2 43± 0 2 5 ) μg/L及(5 5 6 2± 742 ) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 9 6± 2 3 9) μg/L、(2 19± 0 2 9) μg/L及(16 82± 130 )μg/L。(3)对照组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 7 9± 70 7) μg/L、(2 41± 0 36 )μg/L及 (5 5 86± 6 78) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 8 9     

60%氧暴露对早产大鼠肺血管内皮生长因子及其受体表达的影响

目的观察60％氧暴露对早产大鼠肺血管内皮生长因子（vascular endothelial growthfactor，VEGF）及其受体——胎肝激酶-1受体（fetal liver kinase-1，Flk-1）表达的影响，探讨其与新型支气管肺发育不良发病机制之间的关系。方法早产鼠生后6h内随机分为中浓度氧组（简称中氧组）和空气组，空气组置于常压空气中，中氧组置于氧体积分数为60％的氧舱中，两组动物均于生后1、4、7、11和14d各随机取8只，行HE染色，观察肺组织形态学结构，做辐射状肺泡计数（radial alveolar counts，RAC）；采用Western印迹和RT-PCR技术检测各组肺组织VEGF及其受体Flk-1蛋白及mRNA表达水平。结果（1）中氧组RAC在7d时为8．32±0．11，11d时为8．53±0．08，14d时为9．03±0．17，明显高于空气组相应时间点的RAC值；（2）中氧组VEGF及其受体Flk-1 mRNA表达水平在第7、11和14天均低于空气组相应时间点，差异有统计学意义（P〈0．05）；（3）中氧组VEGF蛋白表达水平在第11、14天时低于空气组；受体Flk-1蛋白表达水平与其mRNA表达变化规律基本一致。结论60％氧暴露可引起早产大鼠肺部VEGF及其受体Flk-1表达下降，可能是引起肺微血管发育障碍及肺泡化进程受阻，进而导致新型BPD发生的重要因素。     

胰岛素样生长因子Ⅱ受体在卵巢癌细胞株中的表达及全反式维甲酸对其表达的影响

目的：探讨胰岛素样生长因子Ⅱ受体在卵巢癌细胞中的表达以及全反式维甲酸对其的影响。方法：应用ＮｏｒｔｈｅｒｎＢｌｏｔ技术检测卵巢癌细胞株３Ａｏ，Ａｏ有无胰岛素样生长因子Ⅱ受体以及全反式维甲酸对其的影响。结果：卵巢癌Ａｏ细胞株高表达胰岛素样生长因子Ⅱ受体，３Ａｏ细胞则较低。全反式维甲酸明显引起Ａｏ细胞胰岛素样生长因子Ⅱ受体下降，而３Ａｏ细胞差异不明显。结论：卵巢癌细胞株３Ａｏ和Ａｏ均表达胰岛素样生长因子Ⅱ受体，全反式维甲酸引起Ａｏ细胞株胰岛素样生长因子受体下降，提示胰岛素样生长因子Ⅱ受体参与了全反式维甲酸诱导卵巢癌Ａｏ细胞凋亡过程。     

高氧暴露对早产新生大鼠肺组织凋亡信号调节激酶1表达的影响

目的 研究早产新生大鼠高氧肺损伤肺组织中凋亡信号调节激酶1(apoptosis signalregulating kinase 1,ASK1)及硫氧还蛋白(thioredoxin.Trx)和硫氧还蛋白还原酶(thioredoxin reductase,TrxR)的表达变化及意义,探讨高氧肺损伤的发病机制和防治措施.方法 早产新生SD大鼠128只,生后1 d随机分为空气组和高氧组,每组64只.两组于生后1,4、7、10、14 d各时间点处死8只大鼠取肺组织,采用HE染色观察肺组织病理学变化;采用逆转录一聚合酶链反应技术测定Trx和TrxR mRNA表达;免疫组织化学方法检测肺组织ASK1蛋白的表达和分布,Western印迹法检测ASK1蛋白表达水平变化.两组间比较采用t检验.结果 (1)肺组织病理学:与对照组比较,高氧组肺组织出现明显肺泡炎性改变和肺发育滞后.(2)肺组织ASK1广泛分布于肺泡上皮细胞和血管内皮细胞胞浆中;高氧暴露1、4 d肺组织ASK1蛋白表达分别为0.4382±0.0227和0.5270±0.0432,高于空气组(0.3458±0.0263和0.3760±0.0058)(P<0.01),7 d时下降为0.4343±0.0254,但仍高于空气组(0.3473±0.0220)(P<0.01).(3)高氧组Trx和TrxR mRNA表达强度均高于空气组,且二者分别于10 d(0.6860±0.0811)和7 d(2.0351±0.1600)时达高峰(P<0.05).(4)Western印迹法检测ASK1蛋白水平变化与免疫组织化学法的结果一致.结论 ASK1可能参与高氧肺损伤的发生发展,而Trx系统可能在其中发挥重要保护作用.     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白1表达与妊娠期高血压疾病发病的关系

目的探讨胰岛素样生长因子1(IGF-1)与胰岛素样生长因子结合蛋白1(IGFBP-1)在妊娠期高血压疾病发病中的作用。方法采用酶联免疫吸附法(ELISA)及免疫组化方法检测60例妊娠期高血压疾病患者(妊娠期高血压疾病组,其中妊娠期高血压20例、轻度子痫前期19例、重度子痫前期21例)及18例正常妊娠妇女(对照组)的血清及胎盘组织中IGF-1及IGFBP-1的水平,并分析妊娠期高血压疾病组患者血清中IGF-1水平与胎盘组织中IGFBP-1的相关性。结果(1)血清IGF-1水平:妊娠期高血压疾病组为(229±100)μg/L,明显低于对照组的(336±120)μg/L,两组比较,差异有统计学意义(P<0.01)。妊娠期高血压患者血清中IGF-1水平为(303±80)μg/L,轻度子痫前期患者为(233±77)μg/L,重度子痫前期患者为(155±73)μg/L。3者间比较,差异有统计学意义(P<0.05)。(2)胎盘组织中IGF-1阳性率:妊娠期高血压疾病组为48%(29/60),明显低于对照组的83%(15/18),两组比较,差异有统计学意义(P<0.01);轻、重度子痫前期患者明显低于对照组(P<0.05,P<0.01)。(3)血清中IGFBP-1水平:妊娠期高血压疾病组为(161±90)μg/L,明显高于对照组的(98±75)μg/L,两组比较,差异有统计学意义(P<0.01)。妊娠期高血压患者为(97±73)μg/L,轻度子痫前期患者为(157±69)μg/L,重度子痫前期患者为(225±81)μg/L。3者间比较,差异有统计学意义(P<0.05)。(4)胎盘组织中IGFBP-1阳性率:妊娠期高血压疾病组为77%(46/60),明显高于对照组的39%(5/18),两组比较,差异有统计学意义(P<0.01);轻、重度子痫前期患者明显高于对照组(P<0.05,P<0.01)。(5)相关性:妊娠期高血压疾病组患者血清及胎盘组织中IGF-1水平分别与相应部位的IGFBP-1水平均呈负相关(r=-0.269,P<0.05;r=-0.396,P<0.01)。血清中IGFBP-1水平与胎盘组织中IGFBP-1表达水平呈正相关(r=0.388,P<0.01)。结论孕妇血清及胎盘组织中IGF-1、IGFBP-1水平变化与妊娠期高血压疾病发病及病情发展有关。     

胰岛素样生长因子-Ⅱ和胰岛素样生长因子结合蛋白-1对妊娠早期胚胎发育的影响

目的 探讨胰岛素样生长因子-Ⅱ（insulin-like growth factorⅡ，IGF-Ⅱ）与胰岛素样生长因子结合蛋白1（insulin-like growth factor binding protein-1，IGFBP-1）在妊娠早期对胚胎发育的影响。方法 应用逆转录聚合酶链反应（RT—PCR）、酶联免疫吸附试验（ELISA）分别检测2002-04—2004-01中山大学附属一院47例早孕空胚妊娠妇女（观察组）和38例正常早孕人流妇女（对照组）绒毛组织中的IGF-Ⅱ、蜕膜组织IGFBP-1的mRNA表达量，及母血清中IGFBP-1水平，比较两组数值的相关性。结果 观察组蜕膜组织IGFBP．1mRNA为（3．30±0．32）mg／L，绒毛组织IGF-Ⅱ mRNA为（1．50±0．41）mg／L，母血清IGFBP-1为（50．87±12．08）μg／L；对照组蜕膜组织IGFBP-1 mRNA为（2．14±0．21）mg／L，绒毛组织IGF-Ⅱ mRNA为（3．80±0．17）mg／L，母血清IGFBP-1为（24．31±3．61）μg／L。观察组与对照组间IGF-Ⅱ mRNA、IGFBP-1 mRNA及母血清IGFBP-1比较差异有统计学意义（P〈0．05）；绒毛组织中IGF-Ⅱ mRNA与蜕膜组织中IGFBP-1 mRNA的表达量呈负相关，蜕膜组织IGFBP-1 mRNA与母血清IGFBP-1呈正相关：结论 IGF-Ⅱ、IGFBP-1可能可以作为早期胚胎发育预测潜能的指标，     

角化细胞生长因子在地塞米松干预高氧新生鼠肺组织的表达

目的探讨角化细胞生长因子(keratinocytegrowthfactor,KGF)在高氧新生鼠以及地塞米松干预肺组织的表达与作用。方法将3dSD新生鼠随机分为高氧组(95%氧)、高氧+地塞米松(简称地塞米松组)和正常组;HE染色观察肺组织形态结构,做辐射状肺泡计数;免疫组化检测KGF表达。结果(1)高氧组可见肺泡壁较薄、结构简单化、肺泡大小不均,有些肺泡融合、体积增加,地塞米松组除具有上述高氧组特征外,肺组织结构明显紊乱,部分肺泡壁及间隔破坏;高氧组(9.50±1.05)和地塞米松组(10.03±3.26)辐射状肺泡计数值较正常组(13.00±1.79)减少(P均<0.05)。(2)KGF阳性细胞显色部位在胞浆,显色细胞呈圆形,阳性细胞分布在肺间隔,肺泡周围呈散在分布,靠近支气管处阳性细胞较为集中,有些密集分布。各级支气管及小血管部位未见阳性显色。高氧组和地塞米松组肺组织除了较厚肺间隔偶见散在数个细胞显色外,整个肺组织几乎见不到阳性细胞。结论新生鼠3~10d暴露于高氧环境(95%),可导致肺泡化停滞,肺组织KGF表达被抑制,地塞米松可加重肺部病理改变,KGF表达抑制可能是导致高氧肺发育阻滞的重要因素。     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿生长发育的关系

目的:探讨胰岛素样生长因子1（IGF-1）及胰岛素样生长因子结合蛋白3（IGFBP-3）与胎儿生长发育的关系。方法:应用酶联免疫吸附试验（LISA）测定26例正常妊娠（正常组）,42例妊娠期糖尿病（GDM组）,20例胎儿宫内发育迟缓（IUGR组）孕妇足月剖宫产分娩时,母血与脐血中IGF-1及IGFBP-3的水平,同时记录3组孕妇的新生儿出生体重。结果:（1）母血IGF-1及IGFBP-3的水平正常组分别为18 6.81μg/L、22.82μg/L,GDM组为283.35μg/L、28.29μg/L,IUGR组为220.64μg/L、25.23μg/L,3组间 IGF-IN IGFBP.3水平差异均无显著性（P>0.05）;（2）脐血IGF-1及IGFBP-3的水平正常组分别为62.54μg/L、8.56μg/L,GDM组分别为83.74μg/L、10.21μg/L,IUGR组为37.94μg/L、7.82μg/L,分别进行3组间两两比较,3组IGF-1及IGFBP-3的差异均有显著性（P<0.01）;（3）新生儿平均出生体重正常组为3.22±0.32kg,GDM组为3.76±0.43kg,IUGR组为2.41±0.17kg,3组间两两比较,差异均有显著性（P<0.01）;（4）3组脐血IGF-1及IGFBP-3水平与新生儿出生体重均有显著性正相关（P<0.01）;（5）3组母血及脐血的IGF-1与IGFBP-3均呈显著性正相关（P<0.01）。结论:来自胎儿循环的IGF-1、IGFBP-3对胎儿的生长发育有重要的调节作用,可能参与巨大儿及IUGR的病     

Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 in premature rupture of membranes

BACKGROUND: The aim of the study was to evaluate whether the circulating levels of insulin-like growth factor-I (IGF-I) and its major circulating binding protein, IGFBP-3, are affected in premature rupture of membranes (PROM) and preterm delivery. METHODS: The levels of IGF-I and IGFBP-3 were measured in 32 pregnant women with PROM and in 27 healthy gestational age-matched pregnant women. Statistical analyzes were performed by analysis of variance. RESULTS: All the patients with PROM had preterm delivery, at a gestational age of 31.9 +/- 0.4 weeks (mean +/- SEM). In the control subjects, pregnancy proceeded to term. In the PROM patients, the serum IGF-I and IGFBP-3 levels (289 +/- 21 ng/ml and 8248 +/- 407 ng/ml, respectively) were not statistically different from those in the control subjects (275 +/- 22 ng/ml and 7579 +/- 488 ng/ml). Seventeen patients with PROM showed a rise in serum C-reactive protein, indicating subclinical intrauterine infection. Also in this subgroup of patients the levels of serum IGF-I (281 +/- 27 ng/ml) and IGFBP-3 (9010 +/- 633 ng/ml) were not different from those in the control subjects. Before delivery, serial serum samples were available from 22 patients with PROM. No consistent changes in IGF-I or IGFBP-3 concentrations were seen during the mean follow-up period of 9 days. CONCLUSIONS: IGF-I and IGFBP-3 do not appear to play any significant role in the maintenance of pregnancy in PROM patients with preterm delivery, whether or not associated with emerging intrauterine infection.     

The insulin-like growth factors and feto-placental growth

The insulin-like growth factors, IGF-I and IGF-II, have an important role in fetoplacental growth throughout gestation. They have metabolic, mitogenic and differentiative actions in a wide range of fetal tissues including the placenta. Both Igf1and Igf2genes are expressed in fetal tissues. Expression of the Igf2gene is more abundant than Igf1 gene expression during mid to late gestation. Both IGF's are also present in the fetal circulations with 3-10 fold higher levels of IGF-II than IGF-1 during late gestation. Expression of the Igfgenes is developmentally regulated in a tissue specific manner and can be affected by nutritional and endocrine conditions in utero. Deletion of either Igfgene of the Igf1rgene retards fetal growth while over-expression of IGF-II leads to fetal overgrowth. In mice, placental growth is affected only by manipulation of the Igf2gene. The IGF's also effect the growth of individual fetal tissues and influence the uptake and utilization of nutrients by the fetal and placental tissues. Circulating concentrations and tissue expression of the IGF's are reduced by undernutrition and deficiency of nutritionally sensitive hormones, such as insulin, thyroxine and glucocorticoids. In general, the Igf1gene is more responsive to these stimuli than the Igf2gene. In addition, the effects of the IGFs on feto-placental growth can be amplified or attenuated by the IGF binding proteins, which are themselves regulated by nutritional and endocrine signals. The Igf2gene appears to provide the constitutive drive for intrauterine growth via its placental effects and direct paracrine actions on fetal tissue while the Igf1gene regulates fetal growth in relation to the nutrient supply.     

The expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in mouse placenta

Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) are paracrine regulators of tissue growth and development, and are expressed at the sites of biological action. To study the role of the IGFs and IGFBPs in mouse placental development, we determined the temporal and spatial expression patterns of the mRNAs at embryonic days 10.5 to 18.5 by in situ hybridization. IGF-II mRNA was expressed strongly in mesoderm and fetal blood vessels of early placenta and in labyrinthine trophoblast of later placenta. In the junctional zone, IGF-II mRNA was expressed first in spongiotrophoblasts, later strongly in glycogen cells and variably in giant cells. IGFBP-2 mRNA was expressed weakly in spongiotrophoblasts and glycogen cells. IGFBP-2, -5 and -6 mRNAs were detected in the stroma of the metrial gland. Myometrium expressed IGFBP-2 mRNA strongly, IGFBP-6 mRNA moderately and IGFBP-5 mRNA weakly. The endothelium of maternal blood vessels in decidua expressed IGFBP-3 and -5 mRNAs, and some deeper vessels expressed IGFBP-4 mRNA. In the yolk sac, IGF-II mRNA was expressed in endoderm and mesoderm, whereas IGFBP-1, -2 and -4 mRNAs were expressed only in endoderm, and IGFBP-4 mRNA in mesoderm. Strong expression of IGF-II mRNA in glycogen cells suggests a role in the autocrine/paracrine regulation of invasion. Similar to rat and guinea pig, but in contrast to man and primates, IGFBP mRNAs, except IGFBP-4, were not expressed in mouse decidua. However, IGFBP-3, -4 and -5 mRNAs were expressed in endothelium of maternal blood vessels, and IGFBP-2 and -6 mRNAs in myometrium, where IGFBPs may play a critical role in regulating trophoblast invasion. These findings suggest possible biological roles of the peptides at the feto-maternal interface.     

Effects of dietary advice on insulin-like growth factors among healthy newborns

Objectives

In fetal life, insulin, insulin-like growth factor (IGF) 1, IGF 2 and IGF-binding protein (IGFBP) 3 are essential growth factors. The purpose of this study is to investigate the effects of dietary intervention on insulin-like growth factors in the cord blood of neonates.

Methods

The study involved 52 pregnant women who were followed up in Gazi University Medical School Hospital at Ankara, Turkey. They were randomly divided into two groups: The experimental group was involved in nutrition education. We measured IGF 1, IGF 2 and IGFBP 3 concentrations in cord blood from 52 neonates.

Results

In the experimental group, cord serum levels of IGF 1, IGF 2 were observed to be higher than that of control group.

Conclusion

Dietary advice had positive effects on the cord serum IGF 1 and IGF 2 concentrations. Dietary advice during pregnancy proved to be effective in fetal development.

     

Growth factors in preimplantation development: role of insulin and insulin-like growth factors

In vitro studies of preimplantation embryos from a number of mammalian species have shown that the oviduct and uterus contain growth factors that stimulate cellular proliferation and differentiation of preimplantation embryos. The mammalian preimplantation embryo was first viewed as an autonomous entity, due to the ease with which mouse embryos could be cultured from the two-cell stage on to the blastocyst. This view changed following studies in other species, notably domestic animals, which revealed the presence of 'blocks' to development, when embryos were cultured in vitro. Another line of evidence leading to the view that the maternal environment is crucial for optimal development, was the finding that embryos cultured in vitro lag developmentally behind their in vivo counterparts. This developmental retardation could be ameliorated when washings from the reproductive tract or specific growth factors were added to the media. The expression of genes for growth factors and their receptors is regulated in a tissue-specific manner as well as temporally and spatially during mammalian development. In this review, information regarding the expression and role of polypeptide growth factors of the insulin family during preimplantation mammalian development is summarized.     

基于“治未病”思想观察中药补肾调冲方对卵巢早衰大鼠2种相关生长因子表达的影响

目的 探讨中药补肾调冲方对卵巢早衰(POF)大鼠的防治作用及通过调控血管内皮生长因子(VEGF)、碱性纤维母细胞生长因子(b FGF)的表达调节卵巢功能及预防机制。方法 随机选取SD雌性大鼠60只,分别设空白、模型、中药低、中、高剂量组和西药组,每组10只。空白组自由饮水;模型组给予雷公藤多苷片造模14 d;中药组先给予低、中、高不同剂量补肾调冲中药36 d,再给予雷公藤多苷片造模14 d;西药组先给予结合雌激素36 d,再给予雷公藤多苷片造模14 d。实验结束后观察大鼠的卵巢指数、子宫指数;光学显微镜下计数各组大鼠卵巢内各级卵泡数目;ELISA检测血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、抗苗勒管激素(AMH)的水平;免疫组织化学法检测VEGF及b FGF蛋白的表达;实时荧光PCR法检测VEGF、b FGF m RNA的表达。结果 模型组大鼠卵巢指数、子宫指数明显低于空白组、各给药组(P0.01);中药低剂量组卵巢指数与西药组比较有统计学差异(P0.05);与模型组比较,各给药组及空白组大鼠始基卵泡、窦前卵泡及窦状卵泡数目明显增多,闭锁卵泡的数目明显减少(P0.01);中药低剂量组与西药组比较大鼠始基卵泡、窦前卵泡及窦状卵泡数目明显减少,闭锁卵泡的数目明显增多(P0.05);与模型组比较,各给药组及空白组血清FSH、LH水平明显降低(P0.01),血清E2、AMH水平明显升高(P0.01);与模型组比较,各给药组及空白组VEGF、b FGF蛋白及m RNA表达明显降低(P0.01),中药低剂量组与西药组比较b FGF蛋白表达及m RNA明显降低(P0.05)。结论 中药补肾调冲方对卵巢具有一定的保护作用,预防效果明显,其作用机制可能与补肾调冲方中某些中药能够上调VEGF、b FGF的表达,为卵泡发育提供基础,复苏即将凋亡的卵泡,增强卵巢功能有关。     

Human embryos produce transforming growth factors alpha activity and insulin-like growth factors II.

OBJECTIVE: To assess whether growth factors are produced by early human embryos in culture. DESIGN: We studied various growth factors in the culture media of human embryos (n = 6) cultured from days 3 to 8 after fertilization. MAIN OUTCOME MEASURES: Four growth factors were measured: Insulin growth factors I and II (IGF-I and IGF-II), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) activity. RESULTS: Nonconditioned INRA Menezo B2 (Biomerieux, S.A., Paris, France) culture medium contained significant levels of TGF alpha activity (5.2 ng/mL) and low levels of IGF-I (1.02 ng/mL) and IGF-II (2.8 ng/mL), whereas EGF was below detection of our assay. With human embryo, the culture media contained lower TGF alpha activity on days 3 and 4 after fertilization (2.5 ng/mL and 2.8 ng/mL, P less than 0.05). From days 5 to 8 after fertilization, a significant increase in TGF alpha activity and IGF-II was detected (TGF alpha activity: day 5: 3.7 ng/mL; day 6: 4.4 ng/mL; day 7: 6.4 ng/mL; day 8: 8.4 ng/mL) (IGF-II: day 5: 3.4 ng/mL; day 6: 3.1 ng/mL; day 7: 4.1 ng/mL; day 8: 4.2 ng/mL). Epidermal growth factor was undetectable, and IGF-I did not vary significantly. CONCLUSION: Transforming growth factor alpha activity and IGF-II are produced by human embryos in culture at a time when they could play a role in morula to blastocyst transformation.