胰岛素样生长因子和胰岛素样生长因子结合蛋白在人类胎儿生长中的作用

尽管人类胎儿生长的激素作用机制还不清楚，但研究表明，胰岛素样生长因子（IGFs)和胰岛素样生长因子结合蛋白（IGFBPs)起了重要作用。其中胰岛素样生长因子－1（IGF－1）和胰岛素样生长因子结合蛋白（IGFBP）－3的水平与胎儿的身长和体重呈正相关，而IGFBP－1的水平与胎儿的身长和体重呈负相关。     

胰岛素样生长因子和胰岛素样生长因子结合蛋白在人类胎儿生长中的作用

尽管人类胎儿生长的激素作用机制还不清楚 ,但研究表明 ,胰岛素样生长因子 (IGFs)和胰岛素样生长因子结合蛋白 (IGFBPs)起了重要作用。其中胰岛素样生长因子 1(IGF 1)和胰岛素样生长因子结合蛋白 (IGFBP) 3的水平与胎儿的身长和体重呈正相关 ,而IGFBP 1的水平与胎儿的身长和体重呈负相关     

胰岛素样生长因子—1系统与糖尿病肾病

糖尿病（DM）状态下,肾脏胰岛素样生长因子－1（IGF－1）浓度升高。IGF－1具有刺激系膜基质成分生成,减少系膜细胞中胶原蛋白降解,诱导肾脏中缓激肽和肾素基因表达,并促进系膜细胞产生一氧化氮,增加系膜细胞对葡萄糖的摄入等作用。IGF－1的生物学行为是通过IGF－1受体来介导的,而GF－1与受体间的相互作用是由IGF－1结合蛋白（IGFBP）来调节。DM时,肾脏IGFBP、IGF－1受体水平均发生变化。IGFs通过一个包括IGF－1、IGFBP以及IGF－1受体的复杂系统,在糖尿病肾病的发生发展中起着重要作用。     

胰岛素样生长因子-1系统与糖尿病肾病

糖尿病(DM)状态下,肾脏胰岛素样生长因子-1(IGF-1)浓度升高。IGF-1具有刺激系膜基质成分生成,减少系膜细胞中胶原蛋白降解,诱导肾脏中缓激肽和肾素基因表达,并促进系膜细胞产生一氧化氮,增加系膜细胞对葡萄糖的摄入等作用。IGF-1的生物学行为是通过IGF-1受体来介导的,而IGF-1与受体间的相互作用是由IGF-1结合蛋白(IGFBP)来调节。DM时,肾脏IGFBP、IGF-1受体水平均发生变化。IGFs通过一个包括IGF-1、IGFBP以及IGF-1受体的复杂系统,在糖尿病肾病的发生发展中起着重要作用。     

生长与生长障碍

生长与生长障碍史轶蘩生长和发育是两个不同的生物学概念。生长是生物体形态的增长，是量的变化；发育是器官功能的成熟，是质的改变。一、生长的控制生长的含义包括细胞数目增多（增生）及细胞大小增加（肥大）两个方面。胎儿早期主要是细胞数目增多，以后在不同生长期各...     

肾病综合征患儿的生长激素-胰岛素样生长因子轴的紊乱及意义

随着肾病综合征 (ＮＳ)患儿治愈率和生活质量的提高 ,其生长障碍等问题日益受到关注。为进一步探讨肾病综合征患儿生长障碍的原因及机制 ,前瞻性地研究、防治ＮＳ患儿的生长障碍 ,为改善成年后最终身高提供客观、可靠的数据 ,特对 4 6例不同病理类型的肾病综合征患儿的生长激素 胰岛素样生长因子 (ＧＨ ＩＧＦ)轴的功能状态进行研究 ,报告如下 :一、对象和方法1.研究对象 :ＮＳ患儿 4 6例 ,男 34例 ,女 12例 ,年龄 9～14岁 ,平均 10 .6岁。肾脏穿刺活检病理报告 :系膜增生性肾小球肾炎 (ＭｅｓＰＧＮ) 14例、局灶性肾小球硬化 (ＦＧＳ) 4例…     

过敏性紫癜患儿血清胰岛素样生长因子及胰岛素样生长因子结合蛋白-3的变化

目的 探讨胰岛素样生长因子(IGF)-1及胰岛素样生长因子结合蛋白(IGFBP)-3在过敏性紫癜(HSP)中的作用.方法 采用放射免疫法方法测定45例HSP患儿不同时期的血清IGF-1及IGFBP-3、C反应蛋白(CRP)水平.采用t检验和直线相关关系.结果 HSP急性发作组血清IGF-1[(452±183)μg/L]、IGFBP-3[(13 897±3124)μg/L]及CRP[(20±8)mg/L]水平升高,与健康对照组和缓解组比较,差异均有统计学意义(t值分别为3.42、4.10、11.17、11.63、8.59、9.86.P均<0.01);HSP缓解组血清IGF-1、IGFBP-3及CRP与健康对照组比较,差异无统计学意义(t=0.3,4、0.34、0.52,P均>0.05).HSP急性期并发肾损害组血清IGF-1[(621±253)μg/L]、IGFBP-3[(18 763±3173)μg/L]水平升高,与无肾损害组比较,差异有统计学意义(t值分别为4.21、7.26,P均<0.01),有胃肠道症组血清IGF-1[(479±192)μg/L]、IGFBP-3[(13 986±3162)μg/L]水平与无胃肠道症状组比较,差异无统计学意义(t值分别为0.83、0.16,P均>0.05);血清CRP水平在肾损害组与非肾损害组及胃肠道症组与无胃肠道症状组问差异均无统计学意义(t值分别为0.56、0.32.P均>0.05).HSP急性期患儿血IGF-1、IGFBP-3与CRP浓度之间呈直线正相关(r值分别为0.624,0.672,JP均<0.01).结论 IGF-1、IGFBP-3参与了HSP疾病的病理生理过程,血清IGF-1、IGFBP-3测定对紫癜性肾损害的诊断、病情监测及预后判断有一定帮助.

Abstract：

Objecfive To investigate the role of serum Insulin-like growth factor(IGF)-1,insulinlike growth factor-binding potein(IGFBP)-3 in children with Henoch-Schonlein purpura(HSP).Methods The serum concentration of IGF-1,1GFBP-3 was measured by enzyme-linked immunosorbent assay(ELISA)method in 45 acute SHP patients,40 recoverv patients and 30 healthy controls.Results The serum levels of IGF-1 [(452±183)μg/L],IGFBP-3 [(13 897±3124)μg/L] and C-reactive protein(CRP)[(20±8)mg/L]in acute phase were significantly higher than those in healthy controls(P<0.0 1)and higher than those during recovery period.The serum level of IGF-1,IGFBP-3 for the HSP patients dropped back slowly and their levels during recovery period were the same as those in healthy controls(P>0.05).The serum levels of IGF-1[(621±253)μg/L] and IGFBP-3[(18 763±3173)μg/L] were higher in the renal damage group than in the non-renal damage group(P<0.01).and the same in patients with gastrointestinal symptoms group as in patients without gastrointestinal symptoms group(P>0.05).whereas the serum level of CRP was not significantly different(P>0.05).The serum levels of IGF-1,IGFBP-3 showed positive correlation with the level of CRP(r=0.624,0.672,P<0.01).Conclusion The IGF-1 and IGFBP-3 may play an important role in the pathological mechanism of HSP.The level of IGF-1 may be used as an indicator for HSP disease activity and progression.IGF-1 mav have a close relation with the damage"of renaJ system in HSP.     

急性脑梗死患者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水平的变化

为探讨急性脑梗死患者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水平的动态变化及其临床意义 ,采用酶联免疫吸附试验双抗体夹心法检测 6 0例急性脑梗死患者 (发病后第 3天及第 14天 )和 30例正常人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 ,并根据影像学结果所显示的梗死灶的直径将所有患者分为大梗死组、中梗死组和小梗死组 ,分析梗死灶大小对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水平的影响。结果发现脑梗死组发病后第 3天和第 14天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水平均显著低于正常对照组 (P <0 .0 0 1) ,脑梗死组发病后第 3天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水平显著低于第 14天 (P <0 .0 0 5 ) ;不同大小梗死灶组之间 (发病后第 3天和 14天 )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水平差异显著 (P <0 .0 0 1)。以上提示胰岛素样生长因子 1可能对脑缺血区的神经元具有保护作用 ,而且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水平受梗死灶大小的影响     

胰岛素样生长因子-1与糖尿病肾病关系的研究进展

胰岛素样生长因子-1具有致肾脏肥大和肾小球高滤过,以及使肾脏系膜细胞增生和基质堆积等作用,在糖尿病肾病的发生发展中起一定的促进作用。其机制可能与胰岛素样生长因子系统的紊乱有关。(林栋摘)     

DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP-1) IN EXTREME OBESITY

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)     

THE GROWTH HORMONE INDEPENDENT INSULIN-LIKE GROWTH FACTOR-I BINDING PROTEIN BP-28 IS ASSOCIATED WITH SERUM INSULIN-LIKE GROWTH FACTOR-I INHIBITORY BIOACTIVITY IN ADOLESCENT INSULIN-DEPENDENT DIABETICS

The relationship between the growth hormone independent insulin-like growth factor binding protein (BP-28) and serum insulin-like growth factor-I (IGF-I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics. We have measured the in-vitro effects of purified BP-28 from amniotic fluid on serum IGF-I stimulated and basal cartilage sulphation and compared serum IGF-I bioactivity obtained from 24-h serum profiles from each diabetic subject with serum concentrations of BP-28 and IGF-I measured by specific radioimmunoassays. Purified BP-28 inhibited serum IGF-I stimulated and basal cartilage sulphation in vitro, in a dose-dependent manner. Serum IGF-I bioactivity of diabetic sera showed a change in activity over the 24-h period, with peak inhibitory bioactivity observed in each subject between 0800 and 1000 h. BP-28 concentrations in each individual showed a marked circadian rhythm with maximum peak levels occurring at 0800 h. Long-acting insulin administered in the evening in two of the diabetic subjects blunted the maximum peak level attained compared to the three diabetics who had long-acting insulin administered in the morning. IGF-I concentrations did not change over the 24-h period in each individual. The data shows that BP-28 inhibits serum IGF-bioactivity on cartilage in vitro. The changes in inhibitory bioactivity observed in diabetic serum are associated with similar changes in serum concentrations of BP-28. We propose that BP-28 is one of the IGF-I inhibitors observed in diabetic serum and that it may play a role in retarded growth and delayed puberty often seen in the adolescent diabetic.     

PRODUCTION OF BINDING PROTEINS AND ROLE OF THE INSULIN-LIKE GROWTH FACTOR I BINDING PROTEIN 3 IN HUMAN ARTICULAR CARTILAGE EXPLANTS

The aim of this study was to determine the production of insulin-likegrowth factor binding proteins (IGFBP) and the role of the IGFBP-3in human normal (n = 2) and osteoarthritic (OA) articular cartilage(n = 14) explants. Binding proteins were studied in the mediumby Western ligand blotting and Western blotting. Proteoglycansynthesis under insulin-like growth factor I (IGF-I) stimulationwas studied after a pulse of ³⁵SO^2–₄ in the presence orabsence of added IGFBP-3. Osteoarthritic explants released adoublet of IGFBPs with a 39/43 kDa M_r corresponding to the bindingprotein 3. Constitutive production from unstimulatcd OA cartilagewas higher than from normal cartilage. IGF-1 induced a 20-foldincrease and IL-1 a 2-fold increase in IGFBP-3 release. A minorband around 30 kDa was also detectable. Studies of proteoglycan(PG) synthesis showed that the majority of OA cartilage explantsamples responded weakly to IGF-I (100 ng/ml) stimulation (+33%),while the others were high responders (+180%). Co-incubationof IGF-I with recombinant (r) IGFBP-3 did not affect the rateof PG synthesis. However, while pre-incubation with rIGFBP3for 72 h did not change the rate of PG synthesis in the high-respondergroup, it strongly increased PG synthesis in the low-respondergroup. This study demonstrates that the ability of IGF-I toenhance proteoglycan synthesis varied among the OA samples andmay in part be dependent on the local level of IGFBP-3. Thisimplies pathophysiological considerations in the limits of IGF-Iaction during the OA process. KEY WORDS: Osteoarthritis, Insulin-like growth factor 1, Binding protein 3, Proteoglycan     

慢性充血性心力衰竭患者血、尿β_2微球蛋白和Tamm－Horsfall蛋白测定的意义

对８６例心力衰竭（心衰）患者血、尿β_２微球蛋白和Ｔａｍｍ－Ｈｏｒｓｆａｌｌ蛋白测定结果表明，心衰患者血β_２微球蛋白增高，β_２微球蛋白清除率降低，重度心衰时尿β_２微球蛋白也增高，但β_２微球蛋白排泄分数无改变。血β_２微球蛋白与尿素氮呈正相关、与肌酐清除率呈负相关，而β_２微球蛋白清除率恰与之相反。血、尿Ｔａｍｍ－Ｈｏｒｓｆａｌｌ蛋白随心衰程度的加重而降低。心衰改善后血β_２微球蛋白降低、β_２微球蛋白清除率增高，血、尿Ｔａｍｍ－Ｈｏｒｓｆａｌｌ蛋白也增高。提示血、尿β_２微球蛋白和Ｔａｍｍ－Ｈｏｒｓｆａｌｌ蛋白测定可作为心衰时判断肾功能损害及评价心衰程度的指标。     

肾病综合征大鼠精氨酸血管加压素和V2受体与水孔蛋白-2的研究及黄芪的治疗作用

目的：研究下丘脑精氨酸血管加压素（ Ａ Ｖ Ｐ） 和其 Ｖ２ 受体与 Ａ Ｖ Ｐ 依赖性水通道水孔蛋白２（ Ａ Ｑ Ｐ２ ）在阿霉素肾病综合征大鼠肾脏表达的情况,及中药黄芪对此的影响。　方法：下丘脑 Ａ Ｖ Ｐ ｍ Ｒ Ｎ Ａ 检测用斑点杂交法,肾脏皮髓质 Ａ Ｖ Ｐ Ｖ２ 受体、 Ａ Ｑ Ｐ２ ｍ Ｒ Ｎ Ａ 检测采用半定量 Ｒ Ｔ Ｐ Ｃ Ｒ 法。　结果：肾病大鼠下丘脑 Ａ Ｖ Ｐｍ Ｒ Ｎ Ａ表达较正常对照增强（ Ａ：５３５９ ±５４９ ｖｓ ２５７２ ±１９６ , Ｐ＜ ００１） ,黄芪可纠正此种高表达（ Ａ：２１８８ ±１２５） 。半定量 Ｒ Ｔ Ｐ Ｃ Ｒ 检查发现肾脏皮质和髓质 Ｖ２ 受体、 Ａ Ｑ Ｐ２ ｍ Ｒ Ｎ Ａ 表达均呈现有意义的上调,黄芪则可使这些变化缓解（ Ｐ 均＜ ００１） 。　结论：在阿霉素肾病大鼠中存在下丘脑 Ａ Ｖ Ｐ 基因表达的增加,肾脏 Ａ Ｖ Ｐ Ｖ２ 受体和 Ａ Ｑ Ｐ２ｍ Ｒ Ｎ Ａ 表达的上调,这些变化可能是肾病水潴留的机制之一,中药黄芪能改善这些变化。     

INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-I BINDING PROTEIN IN THE FOLLICULAR FLUIDS OF GROWTH HORMONE TREATED PATIENTS

The presence of GH, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), oestradiol (E2) and progesterone (PG) were investigated in the fluids obtained from various ovarian follicles of seven patients in whom the induction of super-ovulation was achieved only after GH (0.1 U/kg BW/day) was added to the gonadotrophin therapy. The follicular fluids of six patients responsive to treatment with gonadotrophin alone served as a control. In patients treated with combined therapy, the results demonstrated the presence in the follicular fluids of GH (M +/- SEM: 8.5 +/- 0.6 mU/l), E2 (771 +/- 38 nmol/l), and PG (16.4 +/- 0.7 pmol/l) in significantly higher concentrations compared to that in control follicles (6.2 +/- 0.8 mU/l, 681 +/- 30 nmol/l, and 14.4 +/- 0.6 pmol/l; P = 0.002, 0.012, 0.0001 respectively). Acid-extractable IGF-I (143 +/- 9 ng/ml) and EGF (3.9 +/- 0.3 ng/ml) concentrations were similar to those of control fluids (124 +/- 10 ng/ml and 2.9 +/- 0.7 ng/ml respectively) and were highly correlated with each other (P less than 0.001), suggesting a stimulatory effect of EGF on the local IGF-I production. A correlation between GH and IGF-I (n = 51, r = 0.36), as well as between IGF-I and PG (n = 48, r = 0.77) and E2 (n = 48, r = 0.55) was evident only in the follicular fluid of GH-treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

老年慢性充血性心力衰竭患者血清内源性洋地黄样因子的初步研究

30例老年慢性充血性心力衰竭患者和20例正常人用放射免疫法测定血清内源性洋地黄样因子(EDF)浓度。结果显示:老年慢性充血性心力衰竭患者血清EDF浓度明显低于正常;心力衰竭纠正后,血清EDF浓度明显升高;心力衰竭程度、心律失常有无、原发病因、心力衰竭类型对血清EDF浓度无明显影响。     

DIET-INDUCED CHANGES IN SEX HORMONE BINDING GLOBULIN AND FREE TESTOSTERONE IN WOMEN WITH NORMAL OR POLYCYSTIC OVARIES: CORRELATION WITH SERUM INSULIN AND INSULIN-LIKE GROWTH FACTOR-I

The purpose of this study was to investigate the effect of calorie restriction on serum concentrations of sex hormone binding globulin (SHBG) in women with normal or polycystic ovaries (PCO) and to examine the possible role of insulin and insulin-like growth factor-I (IGF-I) in mediating changes in SHBG levels. Six normal subjects with mean (SD) body mass index (BMI) 25.5 (2.2) and five subjects with PCO (BMI 36.1 (3.7)) were studied before and after 2 or (PCO only) 4 weeks of a very low calorie diet (330 kcal/day; Cambridge Diet). In both normal women and patients with PCO there was a twofold increase in SHBG concentrations after 2 weeks and this was sustained in the PCO subjects for a further 2 weeks. The rise in SHBG was accompanied by a fall in free testosterone concentrations. There were parallel changes in serum insulin and IGF-I concentrations which decreased during the diet and there were significant negative correlations of SHBG with insulin in both normal subjects (r = -0.62) and women with PCO (r = -0.60). In addition, serum concentrations of an insulin-dependent small molecular weight (34 kDa) binding protein for IGF-I (IGF-BPI) increased significantly during dieting in both groups and were negatively correlated with serum insulin (controls, r = -0.56; PCO, r = -0.68) and positively correlated with serum SHBG levels (controls, r = 0.69; PCO, r = 0.63). In summary, these data indicate that in both normal subjects and those subjects with PCO, calorie restriction results in a highly significant increase in SHBG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

肿瘤坏死因子及磷脂酶A2与实验性急性肝衰竭

目的：为探讨肿瘤坏死因子（ＴＮＦ）及磷脂酶Ａ＿２（ＰＬＡ＿２）在急性肝衰竭（ＡＨＦ）时的作用及关系。方法：用Ｄ－氨基半乳糖及内毒素复制急性肝衰竭动物模型，检测其血清中ＴＮＦ含量及肝组织匀浆中ＰＬＡ、活性。结果：ＡＨＦ组鼠血清中ＴＮＦ含量及肝组织匀浆中ＰＬＡ＿２活性明显高于正常对照组（Ｐ值＜０．０５，Ｐ值＜０．０１），ＰＬＡ＿２活性与ＴＮＦ含量呈正相关关系。结论：ＴＮＦ可能激活ＰＬＡ＿２，后者与ＴＮＦ所致的肝损伤有关。