IGF-I、OPN、PTEN蛋白在非小细胞肺癌中的表达及其意义

探讨胰岛素样生长因子1(IGF-I)、骨桥蛋白(OPN)和PTEN在人非小细胞肺癌中的表达及其相关性,并分析其与非小细胞肺癌的关系。应用免疫组织化学SP法检测61例肺癌组织和30例癌旁组织中IGF-I、OPN、PTEN的表达情况。结果显示,①肿瘤组织中IGF-I、OPN蛋白表达显著高于癌旁组织(P<0.05),IGF-I的表达与肿瘤分化程度、淋巴结转移有关(P<0.05),OPN的表达与患者肿瘤分化程度、淋巴结转移、TNM分期有关(P<0.05),肿瘤组织中PTEN蛋白表达明显低于癌旁组织(P<0.05),PTEN的表达与肿瘤大小、肿瘤组织的分化程度、有无淋巴结转移有关(P<0.05)。②IGF-I的表达与OPN的表达呈正相关(P<0.05),IGF-I、OPN与PTEN的表达呈负相关(P<0.05)。研究表明,IGF-I、OPN、PTEN蛋白与非小细胞肺癌的发生发展密切相关,三者的表达对判断肺癌恶性程度和预后具有参考意义。     

运动对骨骼肌中胰岛素样生长因子I影响的研究进展

胰岛素样生长因子I(IGF-I)是一类促进细胞生长,具有胰岛素样代谢效应的因子,与运动能力密切相关。分析了近年来关于胰岛素样生长因子在运动、常氧运动、低氧运动不同应激下的变化情况的文献资料。对胰岛素样生长因子研究进展进行了阐述。对于IGF-I与低氧训练关系的研究,有助于提供低氧训练的评定指标,为低氧训练提供科学的理论指导。     

荧光实时定量PCR检测尼罗罗非鱼GH、GHR、IGF-I基因方法的建立及初步应用

 为了准确分析尼罗罗非鱼生长激素（growth hormone , GH）、生长激素受体（growth hormone receptors, GHRs）和胰岛素样生长因子I （Insulin like growth factor-I,IGF I）在早期发育阶段的作用,实验设计了尼罗罗非鱼GH、GHR、IGF I基因的特异性引物,提 取垂体或肝脏总RNA并扩增出目的片段,将PCR产物克隆到pGEM-T Easy载体,经质粒PCR扩增、酶切和测序鉴定重组质粒,构建 标准曲线等,成功建立了GH、GHR、IGF-I基因荧光实时定量PCR检测方法。运用建立的荧光实时定量 PCR检测了尼罗罗非鱼GH 、GHR和IGF I基因表达的发育性变化。结果表明在早期发育阶段,尼罗罗非鱼GH 与 IGF-I,GHR1与 GHR2的mRNA表达存在一 定的互补关系;GH的表达与GHR1的表达呈显著正相关,提示GH与IGF-I,GHR1与GHR2在尼罗罗非鱼早期发育的不同阶段起主导 作用,且GH可能主要通过与GHR1的结合起作用。     

运动对大鼠骨骼肌及血清GH,IGF-I水平研究

生长激素(GH)、胰岛素样生长因子I(IGF-I)都是了解GH-IGF轴变化的主要指标。IGF不仅是内分泌因子,还能在组织局部起作用。通过对6周递增负荷跑台练习的大鼠进行研究,结果显示:运动后即刻处死的大鼠血清GH水平明显升高(P<0.01);运动组与对照组相比,骨骼肌IGF-I水平有明显升高(P<0.01),表明运动对骨骼肌组织内IGF的分泌有调节作用。     

褐牙鲆幼鱼GH、IGF-I、STC、RNA/DNA和糖原含量对盐度操作的响应

对不同盐度胁迫10d后盐度调节至19后恢复期间褐牙鲆(Paralichthys olivaceus)幼鱼血浆生长激素(GH)、类胰岛素生长因子Ⅰ(IGF-I)、司登尼亚钙素(STC)及肌肉和肝脏中RNA/DNA比值和糖原含量变化进行实验监测.结果表明:血浆GH质量浓度在整个实验期间未出现明显差异.IGF-I质量浓度在高盐处理始终较低,只在实验结束时恢复至对照处理水平,而低盐胁迫处理的IGF-I质量浓度则在恢复期间明显高于对照处理.胁迫期间低盐处理STC质量浓度显著低于对照处理和高盐处理,但是在恢复期间恢复至对照组水平;而高盐胁迫处理则下降至显著低于其余两个处理水平.除在胁迫结束时低盐处理的肝脏RNA/DNA高于其余两个处理外,在其他时间肌肉和肝脏的RNA/DNA在不同处理间不存在显著差异.肝脏和肌肉糖原含量在所有时间上不同处理间均不存在显著差异.     

IGF-I、HGF、TGF-β1、IFN-γ对奶牛乳腺上皮细胞增殖活性的影响

研究胰岛素样生长因子-I(IGF-I)、肝细胞生长因子(HGF)、转化生长因子β1(TGF-β1)、干扰素-γ(IFN-γ)对奶牛乳腺上皮细胞体外增殖的调节作用。应用组织块培养和差速消化法获取原代奶牛乳腺上皮细胞,免疫荧光鉴定正确后MTT法评价不同浓度的4种细胞因子对奶牛乳腺上皮细胞体外增殖的影响。IGF-I、HGF分别在10~200 ng/m L,0.1~100 ng/m L浓度范围内对乳腺上皮细胞的增殖呈正相关。而TGF-β1(2.5~100 ng/m L)、IFN-γ(5~160 ng/m L)则剂量依赖性地抑制乳腺上皮细胞增殖。IGF-I、HGF均能促进奶牛乳腺上皮细胞的体外增殖,该作用在一定浓度范围内有剂量依赖性;TGF-β1、IFN-γ对乳腺上皮细胞的增殖作用出现剂量抑制效应。该研究为下一步深入探讨细胞因子对奶牛泌乳机制的研究奠定基础。     

莱芜猪和沂蒙黑猪IGF-I基因的多态性及生长性状的关联性分析

采用PCR-SSCP方法对莱芜猪(127头)和沂蒙黑猪(132头)的胰岛素样生长因子-I(IGF-I)基因exon3和exon4分别进行单核苷酸多态性分析.发现exon3上有多态性,且存在3种基因型(AA、AB、BB).统计结果表明,3种基因型在两品种中的分布不一致,差异极显著(P＜0.01).固定效应模型分析结果表明,初生重、断奶重和6月龄重基因型间差异不显著(P＞0.05).最小二乘分析结果表明,BB基因型与其它2种基因型比较有较大的初生重,同AA和AB型比较差异极显著(P＜0.01),3种基因型在初生重的大小排列顺序为AA＜AB＜BB.因此,推测IGF-I基因对个体的初生重存在一定的影响,选择带有B等位基因的个体,有望提高个体的初生重.     

乐至黑山羊GH和IGF-I基因多态性及其与产羔性状的关联性分析(英文)

生长激素(GH)胰岛素样生长因子I(IGF-I)在卵泡的生长和闭锁中发挥关键作用。研究采用PCR-SSCP技术对157只乐至黑山羊GH和IGF-I进行多态位点的检测。结果发现,GH基因5’侧翼区和第二外显子分别检测到2种基因型,第三外显子检测到4种基因型,第四和第五外显子分别检测到3种基因型;IGF-I基因的第二外显子检测到2种基因型。通过基因测序发现GH基因有14处单核苷酸突变位点(SNPs)—T48C,A55G)(P1引物),T781C(P2引物),G1122A,A1161G,A1171G,C1179T和C1180G(P3引物),T1481C,A1494G,G1549T和C1590T(P4引物),G1942A和G1957A(P5引物);IGF-I基因有1个SNP(G3270C)(P6引物)。关联性分析结果表明,只有GH基因第三外显子BB型乐至黑山羊产羔数比AA型多0.32(p0.05),其余基因型间产羔数差异不显著。研究初步表明GH基因可能与乐至黑山羊产羔数之间存在一定关联性。     

力生长因子与成骨细胞

骨组织对所处的力学环境有极强的适应能力.力学因素及非力学因素共同参与调节骨组织的生长、发育与适应性变化,但是关于两者之间的关联调控目前知之甚少.在骨骼肌肉系统中,IGF-I是一种与力刺激密切相关的骨生长因子.在力刺激作用下,IGF-I的pre-mRNA能选择性的剪接成为力生长因子（Mechano-growth factor,MGF）,MGF具有促进成肌干细胞和成骨细胞增殖,并抑制其终末分化的作用.在力刺激下,MGF参与骨骼肌肉的重建和修复过程.目前初步研究显示MGF主要分布在细胞核,其信号传导不通过IGF-IR介导.但关于MGF的细胞受体,作用靶点、作用机制和信号传导还未得到有效阐明;本文就MGF与骨骼的力学调控之间的关系进行综述.     

半胱胺对鹅生长内分泌的影响

探讨了半胱胺(CS)对成年鹅血浆中生长抑素(SS)、生长激素(GH)和胰岛素样生长因子-I(IGF-I)的影响和调节机理.14只装有翅静脉瘘管的成年杂交鹅(川白×太湖),自身对照.试验期于日粮中一次性添喂半胱胺(100mg/kg,按体重计),自由采食和饮水.采取对照期和处理后第1、3、5、7d的血样,用RIA双抗法测定其中激素的含量.结果表明,试验期SS较对照期(1.89±0.10)μg/L分别降低了41.18%(P<0.01)、26.74%(P<0.01)、37.43%(P<0.01)和17.11%(P<0.05);试验期第1、3、5和7d的GH较对照期(0.55±0.15)μg/L显著(P<0.01)升高,分别为34.55%、78.18%、65.45%和54.55%;试验期的IGF-I较对照期(25.29±4.91)μg/L分别升高了7.28%、59.07%(P<0.01)、22.41%(P<0.05)和1.38%.因此,CS能够降低成年鹅血液中SS含量,使GH和IGF-I水平升高,从而调节鹅的神经内分泌,促进生长.     

Two growth factor signalling pathways in fibroblasts distinguished by pertussis toxin

The primary action of a family of mitogens including bombesin, bradykinin, vasopressin and alpha-thrombin is to activate the hydrolysis of polyphosphoinositides. Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by phospholipase C is mediated through coupling of surface receptors to a GTP-binding protein (Gp protein) which, in some cells, is inactivated by the toxin of Bordetella pertussis. It is not known whether this signalling pathway is involved in initiating DNA replication, whereas it has been firmly established that reinitiation of DNA synthesis can be triggered without activation of PtdIns(4,5)P2 hydrolysis by, for example, EGF (epidermal growth factor), FGF (fibroblast growth factor) and insulin/IGF-I (insulin-like growth factor-I), members of a class of mitogens known to activate receptor tyrosine kinases. Taking advantage of the fact that Chinese hamster lung fibroblasts respond to either class of mitogens and that their Gp protein appears to be sensitive to pertussis toxin, we have now analysed the toxin's effect on reinitiation of DNA synthesis and find that it inhibits up to 95% of thrombin-induced mitogenicity without affecting EGF- or FGF-induced DNA synthesis and proliferation. These findings strongly suggest that activation of PtdIns(4,5)P2-phospholipase C has a determinant function in growth control, and confirm the existence of alternative growth factor-signalling pathways independent of polyphosphoinositide breakdown.     

IGF-1对绵羊皮肤中GHR、IGF-1、IGF-1R、kAP3.2和KAP6-1基因表达的影响

选取36只健康、体况一致的新疆细毛羊随机分成6组。在每只羊的左侧肩胛部皮下局部注射0．5mL（10ng／mL）的IGF-1,右侧肩胛部皮肤为未注射IGF-1的对照组,然后分别于第0、3、6、9、12、50d采集各皮肤样品,用反转录多聚酶链式反应（RT-PCR）方法,定量分析绵羊皮肤中生长激素受体（GHR）、胰岛素样生长因子1（IGF-1）和胰岛素样生长因子1型受体（IGF-1R）、角蛋白关联蛋白KAP3．2和KAP6-1mRNA的相对丰度。试验结果表明,IGF-1对GHR基因的表达有下调的作用,对IGF-1、IGF-1R基因的表达没有显著的影响,而对KAP3．2、KAP6—1基因的表达具有显著的促进作用。说明IGF-1促进绵羊角蛋白关联蛋白基因的表达可能是通过生长轴以外的其他途径实现的。     

早期胚胎体外培养相关细胞因子研究进展

综述了五种细胞因子(表皮生长因子,转化生长因子,白血病抑制因子,胰岛素样生长因子和血管内皮生长因子)对于克服哺乳动物早期胚胎发育阻滞发挥的积极作用.     

Relationships among magnetic resonance imaging, histological findings, and IGF-I in steroid-induced osteonecrosis of the femoral head in rabbits

Objective: To study the relationships among magnetic resonance imaging (MRI), histological findings, and insulin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits. Methods: Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I. Results: At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific “line-like sign”. The MRI findings of all femora in Group B were normal. Conclusion: MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies.     

Insulin-like growth factor II receptor as a multifunctional binding protein

The primary structure of human insulin-like growth factor II receptor, predicted from the complementary DNA sequence, reveals a transmembrane receptor molecule with a large extracellular domain made up of fifteen repeat sequences and a small region homologous to the collagen-binding domain of fibronectin. The structural and biochemical features of the IGF-II receptor appear identical to those of the cation-independent mannose-6-phosphate receptor.     

Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor

Many of the actions previously attributed to pituitary-derived growth hormone are mediated by polypeptide growth factors. These include the insulin-like growth factors I and II (IGF-I and IGF-II), which are members of the insulin family of proteins. We report here the chromosomal mapping of the human genes for IGF-I and IGF-II. IGF-II maps to the short arm of chromosome 11, which also contains the gene for insulin and the proto-oncogene c-Ha-ras1 (ref. 9). IGF-I maps to chromosome 12, which is evolutionarily related to chromosome 11 and carries the gene for the proto-oncogene c-Ki-ras2 (refs 10,44). We have also localized the human gene for an unrelated polypeptide hormone, epidermal growth factor, to chromosome 4q, in the same region as another specialized growth factor, T-cell growth factor. We speculate that these map assignments reflect the existence of gene families involved in growth control.     

Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I

Insulin-like growth factor I (IGF-I) and insulin stem from a common precursor, are structural homologues, act through similar receptors and elicit insulin-like and growth-promoting effects in vitro and in vivo. Serum IGF-I levels are controlled by growth hormone, insulin and nutrition. Insulin-deficient growth-arrested diabetic animals have reduced serum IGF-I levels which are restored towards normal by insulin but not by growth-hormone treatment. Here we show that normal growth of diabetic rate is restored by infusion of recombinant human (rh)IGF-I without normalization of the blood sugar level and that insulin acts via an increase of IGF-I synthesis on growth of diabetic rats. We describe a new mechanism of endocrine control of growth in which IGF-I is the major stimulator at the cellular level. Growth hormone and insulin act mainly by modulating the hepatic synthesis of IGF-I.