叶酸缺乏孕鼠子代脑组织DNA甲基化水平的变化

目的 :探讨叶酸缺乏对胎鼠宫内脑发育的影响 ,研究叶酸缺乏孕鼠子代脑组织基因组DNA甲基化水平的改变 ,为叶酸缺乏造成脑发育障碍提供分子和细胞水平的依据。方法 :雌性SD大鼠实验组 30只、对照组 2 0只 ,分别饲以不含叶酸和含 2mg叶酸 kg的纯合饲料 ,两周后与雄鼠交配 ,于怀孕第 2 0天对孕鼠剖腹取胎。对模型进行评价并观察叶酸缺乏对胎鼠发育的影响 ,高效液相色谱法检测胎鼠脑组织基因组DNA甲基化水平。对孕鼠妊娠晚期末血清叶酸、胎鼠血清叶酸及胎鼠脑组织DNA甲基化水平作相关分析。结果 :1 实验组孕鼠交配前及妊娠晚期末血清叶酸均明显低于对照组 ,外周血出现多分叶核粒细胞。实验组胎鼠血清叶酸也明显低于对照组 ,出现巨幼红细胞 ,RBC和Hb均低于对照组 ,且伴有宫内生长限制。 2 实验组胎鼠脑组织基因组DNA甲基化水平低于对照组 ,这种改变与孕鼠及胎鼠本身的血清叶酸浓度呈正相关。结论 :1 交配前两周开始限食叶酸直至妊娠期结束 ,所建立的叶酸缺乏孕鼠动物模型处于叶酸缺乏第三阶段 ,其胎鼠宫内生长受限制 ,红细胞出现巨幼变 ,但没有产生神经管闭合的异常。这是较理想的妊娠中晚期叶酸缺乏的大鼠动物模型。 2 母体叶酸缺乏时胎鼠的脑组织基因组DNA甲基化水平降低 ,这种改变与孕鼠及胎鼠本身的     

叶酸缺乏孕鼠子代脑组织DNA甲基化水平的变化

目的：探讨叶酸缺乏对胎鼠宫内脑发育的影响，研究叶酸缺乏孕鼠子代脑组织基因组DNA甲基化水平的改变，为叶酸缺乏造成脑发育障碍提供分子和细胞水平的依据。方法：雄性SD大鼠实验组30只、对照组20只，分别饲以不含叶酸和含2mg叶酸/kg的纯合饲料，两周后与雄鼠交配，于怀孕第20天对孕鼠剖腹取胎。对模型进行评价并观察叶酸缺乏对胎鼠发育的影响，高效液相色谱法检测胎鼠脑组织基因组DNA甲基化水平。对孕鼠妊娠晚期末血清叶酸、胎鼠血清叶酸及胎鼠脑组织DNA甲基化水平作相关分析。结果：1．实验组孕鼠交配前及妊娠晚期末血清叶酸均明显低于对照组，外周血出现多分叶核粗细胞。实验组胎鼠血清叶酸也明显低于对照组，出现巨幼红细胞，RBC和Hb均低于对照组，且伴有宫内生长限制。2．实验组胎鼠脑组织基因组DNA甲基化水平低于对照组，这种改变与孕鼠及胎鼠本身的血清叶酸浓度呈正相关。结论：1．交配前两周开始限食叶酸直至妊娠期结束，所建立的叶酸缺乏孕鼠动物模型处于叶酸缺乏第三阶段，其胎鼠宫内生长受限制，红细胞出现巨幼变，但没有产生神经管闭合的异常。这是较理想的妊娠中晚期叶酸缺乏的大鼠动物模型。2．母体叶酸缺乏时胎鼠的脑组织基因组DNA甲基化水平降低，这种改变与孕鼠及胎鼠本身的血清叶酸浓度呈正相关，可能是母体叶酸缺乏时胎鼠脑发育障碍的机制之一。3．受孕前后增补叶酸宜延长至妊娠结束，以减少不良妊娠结局的危险。     

叶酸缺乏孕鼠子代血细胞形态学改变及脑额区皮层超微结构表现

探讨叶酸缺乏对胎鼠宫内脑发育的影响、研究叶酸缺乏孕鼠子代胎鼠脑组织超微结构的改变及为叶酸缺乏造成脑发育障碍提供细胞水平的依据 ,及采用雌性SD大鼠实验组 30只、对照组 2 0只 ,分别饲以不含叶酸和含 2mg叶酸 kg的纯合饲料 ,两周后与雄鼠交配 ,于怀孕第 2 0天对孕鼠剖腹取胎 ,对模型进行评价并观察叶酸缺乏对胎鼠发育的影响 ,应用透射电镜观察胎鼠额区皮层超微结构的改变。结果显示 :1 .实验组孕鼠交配前及妊娠晚期末血清叶酸均明显低于对照组 ,外周血出现多分叶核粒细胞。实验组胎鼠血清叶酸也明显低于对照组 ,出现巨幼红细胞 ,RBC和HB均低于对照组 ,且伴有宫内生长限制。 2 .实验组胎鼠额区皮层超微结构观察示 :神经元出现核切迹、局灶性核周腔扩张、异染色质减少、胞质内细胞器肿胀、核糖体减少 ;某些胶质细胞亦见类似改变 ;神经毡膜性结构不完整。结论 :1 .交配前两周开始限食叶酸直至妊娠期结束 ,所建立的叶酸缺乏孕鼠动物模型处于叶酸缺乏第三阶段 ,其胎鼠宫内生长限制 ,红细胞出现巨幼变 ,但没有产生神经管闭合的异常。这是较理想的妊娠中晚期叶酸缺乏的孕鼠动物模型。 2 .母体叶酸缺乏能造成胎鼠皮层脑组织超微结构的改变 ,可能导致神经元功能的紊乱和丧失 ,以致防碍脑结构和脑功能的正?     

DEHP诱导的隐睾鼠胰岛素样因子3基因CpG岛甲基化状态研究

目的 研究胰岛素样因子3(insulin-like factor 3,INSL3)基因在邻苯二甲酸二已酯(DEHP)致小鼠隐睾中DNA甲基化的状态.方法 运用"MethPrimer"软件对INSL3基因进行分析.预测CpG岛,通过甲基化特异性PCR(methylation-specific PCR,MS-PCR)检测INSL3基因CpG岛的甲基化状况,并应用RT-PCR检测INSL3基因在正常组与实验组睾丸组织中的表达情况.结果实验组INSL3基凶第一外显子区存在CpG岛甲基化;实验组INSL3基因mRNA表达显著下降.结论 INSL3基因第一外显子区CpG岛的异常甲基化导致INSL3在隐睾鼠睾丸中表达降低,可能与隐睾的发生密切相关.     

叶酸缺乏孕鼠子代血细胞形态学改变及脑额区皮层超微结构表现

探讨叶酸缺乏对胎鼠宫内脑发育的影响、研究叶酸缺乏孕鼠子代胎鼠脑组织超微结构的改变及为叶酸缺乏造成脑发育障碍提供细胞水平的依据，及采用雌性SD大鼠实验组30只、对照组20只，分别饲以不含叶酸和含2mg叶酸/kg的纯合饲料，两周后与雄鼠交配，于怀孕第20天对孕鼠剖腹取胎，对模型进行评价并观察叶酸缺乏对胎鼠发育的影响，应用途射电镜观察胎鼠额区皮层超微结构的改变。结果显示：1．实验组孕鼠交配前及妊娠晚期末血清叶酸均明显低于对照组，外周血出现多分叶核粒细胞。实验组胎鼠血清叶酸也明显低于对照组，出现巨幼红细胞，RBC和HB均低于对照组，且伴有宫内生长限制。2．实验组胎鼠额区皮层超微结构观察示：神经元出现核切迹、局灶性核周腔扩张、异染色质减少、胞质内细胞器肿胀、核糖体减少；某些胶质细胞亦见类似改变；神经毡膜性结构不完整。结论：1．交配前两周开始限食叶酸直至妊娠期结束，所建立的叶酸缺乏孕鼠动物模型处于叶酸缺乏第三阶段，其胎鼠宫内生长限制，红细胞出现巨幼变，但没有产生神经管闭合的异常。这是较理想的妊娠中晚期叶酸缺乏的孕鼠动物模型。2．母体叶酸缺乏能造成胎鼠皮层脑组织超微结构的改变，可能导致神经无功能的紊乱和丧失，以致防碍脑结构和脑功能的正常发育。3．受孕前后增补叶酸宜延长至妊娠结束，以减少不良妊娠结局的危险。     

胰岛素样生长因子与生长发育的研究进展

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，在儿童生长发育中起重要作用。IGFs通过自分泌和旁分泌机制对肌母细胞、成骨细胞、脂肪细胞、神经细胞、造血细胞等的增殖分化起调节作用；IGFs还能促进蛋白质的合成、葡萄糖氧化与脂肪分解；同时促进免疫细胞的分化与成熟，保护肠道黏膜屏障，提示重组IGFs可用于疾病的治疗。     

胰岛素样生长因子结合蛋白2在新生鼠肺发育中的作用

目的探索胰岛素样生长因子结合蛋白(IGFBP)2在新生鼠肺发育中的作用。方法SD孕鼠80只分为4组,即A:对照组;B:地塞米松(Dex)1组;C:Dex2组;D:维A酸(RA)组。A、B、D组分别于孕18～20d皮下注射生理盐水、Dex,腹腔注射RA;C组于生后1～3d皮下注射Dex。各组分别于孕18、20、21d(C组孕期不取)、生后1、3、5、7、10、14、21d取肺标本作形态学检查、免疫组织化学、Westernblot及RT PCR检测。结果1.肺组织形态学:B、C组早期肺泡发育提前,数目多,壁薄,晚期则明显落后于A、D组。2.IGFBP2肺表达:A组中IGFBP2主要在胎肺组织中表达,孕18d左右表达最强,随后表达渐减弱。B、C组表达趋势同A组,但生后各时间点均较A组增强;D组生后各时间点均较A组减弱。3.Westernblot:IGFBP2多肽表达强度各组孕18d表达最强,随后渐降低;B、C组生后各时间点表达强度明显高于A组(P均<0.01);D组各时间点浓度均明显低于A组(P均<0.01)。4.RT PCR:IGFBP2mRNA表达的强度变化规律与其肽浓度变化相似。结论IGFBP2在肺发育过程起重要作用,其浓度过高则影响肺发育。     

胰岛素样生长因子与生长发育的研究进展

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 ,在儿童生长发育中起重要作用。IGFs通过自分泌和旁分泌机制对肌母细胞、成骨细胞、脂肪细胞、神经细胞、造血细胞等的增殖分化起调节作用 ;IGFs还能促进蛋白质的合成、葡萄糖氧化与脂肪分解 ;同时促进免疫细胞的分化与成熟 ,保护肠道黏膜屏障 ,提示重组IGFs可用于疾病的治疗     

长期吸入糖皮质激素对支气管哮喘儿童胰岛素样生长因子的影响

吸入糖皮质激素是目前哮喘治疗和预防的一线方案。临床资料表明吸入激素治疗哮喘有效熏但由于糖皮质激素存在的诸多不良反应,特别是对生长发育的影响,使许多医师、患者及家属对此产生很多顾虑,不敢长期使用,以至于影响治疗效果。国内外许多学者进行了大量临床研究工作,已经证实     

叶酸缺乏对孕鼠子代心脏中NKx2.5基因表达的影响

目的探讨叶酸缺乏孕鼠子代心脏发育过程中NKx2.5基因和蛋白表达改变。方法成熟雌性36只SD大鼠随机分为实验组和对照组各18只,分别喂以缺乏叶酸和添加叶酸的纯合饲料。2周后与成熟SD雄性大鼠交配,分别取孕13.5 d、孕17.5 d胚胎鼠及新生鼠心脏。用RT-PCR检测NKx2.5基因mRNA表达。Western-blotting测GATA-4蛋白表达水平。结果NKx2.5基因mRNA及其蛋白在孕13.5 d、孕17.5 d胚胎心脏及新生鼠心脏中的表达量,实验组均显著低于对照组(P均<0.05)。结论叶酸缺乏影响NKx2.5基因和蛋白表达水平,可能导致心脏发生发育中形态改变,从而造成心脏功能缺陷。     

Effects of recombinant human insulin-like growth factor I administration in adults with growth hormone deficiency

Recombinant human insulin-like growth factor I (IGF-I), 40 μg/kg/body weight, was administered subcutaneously at 08.00 hours to six adult patients with growth hormone deficiency (GHD). The mean maximal IGF-I concentrations were found 2–6 hours after injection. Concentrations then gradually declined, though mean values were still above basal 24 hours after the injection. Only one patient maintained IGF-I levels above the lower normal range throughout 24 hours. There was a significant decrease in mean IGF-II concentrations when measured 4 and 24 hours after injection of IGF-I. The diurnal variations of insulin and IGF binding protein-1 were preserved. There were no side-effects, and blood glucose remained normal. These results show that in patients with low IGF-I levels resulting from GHD, it is necessary to administer IGF-I at intervals of less than 24 hours to obtain IGF-I levels that are within the normal range.     

L-精氨酸对宫内发育迟缓胎鼠胰岛素样生长因子及其结合蛋白表达的影响

目的：宫内发育迟缓(IUGR)儿常有脑发育的异常,L精氨酸具有舒张血管、增加胎盘血流的作用,可用于改善胎盘缺氧状态,促进胎儿生长发育。用被动吸烟法制作孕鼠IUGR模型,孕8～20d给予不同剂量L精氨酸,了解其对宫内发育迟缓胎鼠脑内胰岛素样生长因子及其结合蛋白表达的影响,并探讨L精氨酸的作用机制。方法：孕鼠随机分为4组:对照组、模型组、L精氨酸小剂量和大剂量防治组,每组9只。孕21d剖宫取胎,应用酶联免疫吸附法检测各组胎鼠脑组织胰岛素样生长因子Ⅰ(IGFⅠ)、胰岛素样生长因子Ⅱ(IGFⅡ)、胰岛素样生长因子结合蛋白(IGFBP3)含量,应用荧光定量RTPCR法检测各组胎鼠脑组织IGFⅠmRNA表达。结果：与对照组相比较,模型组胎鼠脑组织中IGFⅠ(0.789±0.062ng/mgvs0.947±0.042ng/mg)、IGFⅡ(0.270±0.020ng/mgvs0.374±0.015ng/mg)含量均比对照组明显降低,IGFBP3(0.253±0.011ng/mgvs0.089±0.015ng/mg)含量比对照组明显升高,IGFⅠmRNA表达量(13.12±1.39)×104cps/μgRNAvs(21.28±3.54)×104cps/μgRNA比对照组明显降低,差异均有显著性(P<0.01)。与模型组相比较,小剂量和大剂量L精氨酸防治组IGFⅠ含量明显增高,分别为0.937±0.067ng/mg和0.858±0.077ng/mg,IGFⅡ含量明显增高,分别为0.318±0.018ng/mg和0.354±0.021ng/mg,IGFBP3含量明显降低,分别为0.132±0.006ng/mg和0.146±0.009ng/mg差异有显著性(P<0.01或<0.05)。同时小剂量和大剂量L精氨酸防治组IGFⅠmRNA表达量也明显增高,分别为(19.24±2.48)×104cps/μgRNA和(17.35±2.30)×104cps/μgRNAvs(13.12±1.39)×104cps/μgRNA,差异均有显著性(P<0.01)。结论：L精氨酸可增加被动吸烟致宫内发育迟缓胎鼠脑内IGFⅠ、IGFⅡ含量和IGFⅠmRNA的表达,降低IGFBP3含量。L精氨酸防治IUGR的机制与其对胰岛素样生长因子及其结合蛋白表达的影响有关。     

Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II among the IGF binding proteins (IGFBPs) was studied before and during IGF-I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30–35% of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF-I and the decrease in IGF-II were proportional. Similarly, serum concentrations of IGFBP-3 and the acid-labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.     

Serum levels of insulin-like growth factor-I,-II and insulin-like growth factor binding proteins-2 and-3 in children with acute lymphoblastic leukaemia

Abstract The insulin-like growth factor (IGF) signaling pathway may be of importance for the proliferation of different tumours (e.g. breast cancer and Wilms tumour). The bioavailability of both IGF-I and IGF-II is regulated by specific IGF-binding proteins (IGFBPs). IGFBP-2 is the predominant binding protein during fetal life, where it is expressed in most tissues. In contrast, postnatally it is mainly released by specific cell types (hepatocytes, astroglia, kidney cells, prostate cells) and a range of tumour cell lines. Furthermore, phytohaemagglutinin stimulated normal lymphoblasts and malignant lymphoblasts express IGFBP-2. In order to investigate the IGF regulatory pathway in leukaemia serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in 28 leukaemic children. Whereas serum levels of IGF-I (mean/range: –2.7/–0.1 to –6.7 SDS), IGF-II (–3.6 SDS/–1.3 to –8.7) and IGFBP-3 (–2.0/+2.2 to –7.1 SDS) were significantly decreased comparable to levels in growth hormone deficiency, IGFBP-2 levels (+4.0/–0.45 to +7.4 SDS) were found to be markedly elevated and inversely correlated to IGF-I (r=–0.51,P=0.013). After haematological remission upon chemotherapy all four parameters had normalized in the 16 re-investigated children. Similar findings have been observed in one boy with a relapse including CNS leukaemia.Conclusion This study demonstrates that the proliferation of malignant lymphoblasts (at diagnosis vs treatment) occurs in the presence of decreased serum levels of IGF-I, IGF-II and IGFBP-3 and that diminished production of these peptides may contribute to impaired growth. It further indicates that serum levels of IGFBP-2 may be directly related to the proliferation of lymphoblasts.     

性早熟女性患儿血清IGF-1和IGFBP-3质量浓度检测及临床价值

目的　探讨女性特发性中枢性性早熟(ICPP)及乳房早发育患儿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 )的关系及临床意义。方法　以放射免疫法测定于2 0 0 0年5月至2 0 0 4年1月在暨南大学医学院第二附属医院就诊的2 2例ICPP及2 8例乳房早发育女孩血清IGF- 1和IGFBP -3的水平,并以2 5名正常青春发育期女孩及3 0名未发育女孩作为对照,以IGF- 1、IGFBP- 3为诊断指标,对ICPP进行诊断试验评价。结果　ICPP女性患儿血清IGF -1、IGFBP- 3水平均明显高于乳房早发育及未发育女孩(P <0 .0 1 ) ,而与正常青春发育女孩差别无显著性意义(P >0 .0 5)。IGF- 1 >2 69 .1 4mg/L对诊断ICPP的灵敏度、特异度、阳性预测值、准确度分别为95% ,96% ,95% ,96% ;IGFBP -3 >3 53 6 42mg/L对诊断ICPP的灵敏度、特异度、阳性预测值、准确度分别为72 % ,96% ,94% ,86%。结论　ICPP女性患儿血清IGF 1、IGFBP- 3水平明显增高,IGF -1、IGFBP -3对鉴别ICPP与乳房早发育具有临床意义。     

Pharmacokinetics of recombinant human insulin-like growth factor I given subcutaneously to healthy volunteers and to patients with growth hormone receptor deficiency

The pharmacokinetics of recombinant human insulin-like growth factor I (rhIGF-I) were studied in healthy volunteers and in patients with growth hormone receptor deficiency (GHRD; Laron syndrome). Following single subcutaneous injections of rhIGF-I, 40 and 80 μgkg, to healthy volunteers, the peptide was absorbed slowly, with a maximum concentration reached after about 7 hours. Following daily multiple subcutaneous injections of rhIGF-I, 40 μg/kg, trough concentrations of IGF-I were increased by 277 ± 50 μg/l (mean ± SD) from baseline. IGF-I was thus characterized as a low-clearance peptide, with a clearance and half-life estimated at about 0.20 ml/minute/kg and 20 hours, respectively, in healthy volunteers. The volume of distribution was low, about 0.20–0.36 litres/kg, the bioavailability of subcutaneously administered rhIGF-I was 100%, and the rate of production of IGF-I was estimated to be about 50 μg/kg/day (3.5 mg/day). Patients with GHRD had low baseline IGF-I concentrations (30–50 μ g/ l) and a much more rapid turnover of IGF-I compared with that in healthy volunteers. The clearance and half-life of IGF-I were estimated to be about 0.60 ml/minute/kg and 6 hours, respectively. The volume of distribution was about the same as in healthy subjects. Due to the rapid turnover of IGF-I, trough IGF-I concentrations were increased to just above baseline during subcutaneous injections of 40 μg/kg once daily for 7 days. The maximum increase in IGF-I levels was 111 ± 12 μg/l and 150 ± 3 μg/l following daily subcutaneous injections of 40 × 1 and 40 × 2 μg/kg for 7 days, respectively.     

胰岛素样生长因子1对新生儿脐带血单个核细胞产生细胞因子？…

目的 研究胰岛素样生长因子１（ＩＣＦ－１）对新生儿免疫功能的影响。方法 利用无血清、无激素培养系统,体外培养１０例健康足月顺产儿脐带血单个核细胞（ＣＢＭＣ）。１０例健康成人外周血单个核细胞（ＰＢＭＣ）为正常对照,观察ＩＧＦ－１对ＣＢＭＣ细胞因子产生的影响。结果 与正常组比较,植物血凝素（ＰＨＡ）诱导的ＣＢＭＣＩＬ－２、ＩＬ－４、干扰素γ（ＩＦＮ－γ）、ＩＬ－１０和ＩＬ－１２水平显著低下（Ｐ值均〈０     

Good growth despite very low levels of insulin-like growth factors

A 12.5-year-old girl presented with short stature. Insulin-like growth factor 1(IGF-I) and insulin- like growth factor binding protein (IGFBP-3) were below the 0.1 percentile. Growth hormone provocation tests disclosed normal responses to l-arginine and insulin-induced hypoglycaemia. A huge benign mesenteric cyst was discovered by abdominal ultrasound and completely removed. Subsequently, the girl showed a marked catch-up growth; however, IGF-I and IGFBP-3 remained below the 0.1 percentile. Conclusion These observations imply that growth may take place even with very low levels of insulin-like growth factors. The interpretation of low IGF-I and IGFBP-3 levels in short children still requires good clinical judgement and basic knowledge of their biological action. Received: 24 September 1997 / Accepted in revised form: 16 March 1998     

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。     

Inflammation at birth and the insulin-like growth factor system in very preterm infants

BACKGROUND: Foetal inflammation is associated with an increased risk of brain damage in preterm infants whereas IGF-I is essential for cerebral development and exhibits anti-apoptotic properties. AIM: To assess levels of IGF-I and IGF binding proteins at very preterm birth and to evaluate their relationship with foetal pro-inflammation and cerebral damage. METHODS: Levels of IGF-I, IGF binding protein 3 (IGFBP-3), high- (hp) and low-phosphorylated (lp) IGFBP-1 in cord blood and neonatal blood at 72 h after delivery were analysed in relation to levels of cytokines and cerebral damage as detected by ultrasound in 74 inborn infants [mean gestational age (GA) 27.1 weeks]. Evaluation was performed separately according to birth weight for GA. RESULTS: In cord blood of infants appropriate for gestational age (AGA) higher levels of IL-6 and IL-8 were associated with lower IGF-I (r =-0.38, p = 0.008 and r =-0.36, p = 0.014). Higher levels of IL-6, IL-8 and TNF-alpha were associated with both higher levels of lpIGFBP-1 (r = 0.54, p < 0.001, r = 0.50, p < 0.001 and r = 0.13, p = 0.012, respectively) and hpIGFBP-1 (r = 0.55, p < 0.001, r = 0.45, p = 0.002 and r = 0.32, p = 0.026, respectively). Infants with intraventricular haemorrhage grade III (n = 5) had higher levels of lp/hpIGFBP-1 in cord blood (p = 0.001 and 0.002, respectively). CONCLUSION: Pro-inflammation at birth is associated with changes in the IGF-system. This may be of importance for development of brain damage in preterm infants.