胰岛素样生长因子
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类胰岛素样生长因子测定标准值概述说明1. 引言1.1 概述类胰岛素样生长因子(IGF)是一种重要的蛋白质激素,与细胞增殖、分化和存活密切相关。
它是由下丘脑垂体前叶分泌的生长激素刺激产生的,主要存在于血液中,并通过与其相互作用的IGF结合蛋白进行调控。
IGF在人体内发挥着多种生物学功能,包括对组织生长和代谢的调节,以及参与疾病的发展过程。
1.2 文章结构本文将按照以下方式进行介绍:首先,我们将介绍胰岛素样生长因子的定义和作用;接着,我们将详细介绍测定胰岛素样生长因子的方法和技术;然后,我们会探讨类胰岛素样生长因子的重要性及其参考范围;接下来,我们将展示研究方法与结果分析部分,包括实验设计和样本选择、测定类胰岛素样生长因子标准值的步骤和流程等内容;随后,我们将讨论影响类胰岛素样生长因子测定标准值的因素,包括年龄和性别、健康状况和慢性疾病以及其他可能的影响因素;最后,我们将总结本研究的主要发现,并展望类胰岛素样生长因子测定标准值研究的未来发展。
1.3 目的本文旨在系统地介绍测定类胰岛素样生长因子(IGF)的标准值,并讨论影响其测定结果的因素。
通过对胰岛素样生长因子在人体内的作用机制进行深入了解和分析,可以为临床医生和研究人员提供指导,并推动该领域进一步发展。
2. 正文:2.1 胰岛素样生长因子的定义和作用胰岛素样生长因子(IGF)是一种由肝脏合成并通过循环系统分泌的多肽激素,主要由胰岛β细胞和其他组织产生。
IGF具有类似胰岛素的结构和功能,可通过与细胞表面的IGF受体结合,促进细胞增殖、分化和存活。
它在机体发育、生长、代谢调控以及多种疾病的发展中起到重要作用。
2.2 测定胰岛素样生长因子的方法和技术目前常用于测定血清中胰岛素样生长因子水平的方法包括放射免疫测定法、酶联免疫吸附法等。
放射免疫测定法利用放射性同位素标记的抗体对IGF进行检测;而酶联免疫吸附法则是利用酶偶联抗体对IGF进行定量分析。
这些方法及技术具有灵敏度高、准确度较高等特点。
胰岛素样生长因子(Insulin-like growth factor)Insulin-like growth factorBasic conceptShanghai Ya Xi (International) snow America authorized biomedical technology services center marketing P DepartmentInsulin-like growth factors (IGFs) is a class of multifunctional cell proliferation regulating factors. It plays an important role in cell differentiation, proliferation and individual growth and development. This paper reviews the general situation of IGFs and its relationship with growth and development.History of IGFSGrowth hormone and Daughaday on 1957 Salmon (growth hormone, referred to as GH) in the process of giving first found in hypophysectomized rats after GH serum can stimulate S into cultured cartilage, but directly into the liquid culture of GH has no effect, so that GH itself can directly stimulate the growth of cartilage, but through a "SF" role, this factor became known as growth regulator. 1963 Froesh found in the serum insulin like effect on muscle and fat cells are only a small part of the insulin antiserum inhibited the remaining soluble insulin like activity was not inhibited in acidified ethanol, and named NSILAS which is inhibited by insulin like activity (nonsuppressible insulin-like activity). In 1972, Pieron and Temin purified a cytokine from bovine serum that stimulated cell division, called proliferation stimulating activity".After the above three experiments were completed, it was found that the above three substances had an inhibitory insulin-like activity and a growth stimulatory effect. With the development of molecular biology, 1978 people purified two kinds of NSILA (I, II) and found its structure and proinsulin were named as similar, insulin-like growth factor I and II (IGF I, II) to emphasize their homology with insulin structure. It was also confirmed that the sulfation factor and the proliferation stimulating activity were members of the same polypeptide family as IGF.Composition, physical and chemical properties of IGFs systemThe IGFs family is composed of two low molecular polypeptides (IGF-, I, IGF- II), two specific receptors and six binding proteins. IGF- I is a single nucleotide protein with 70 amino acids, the molecular weight of 7649Da, heat resistance, while IGF- II is a single stranded weak acid protein with 67 amino acids, with a molecular weight of 7471Da and stable for 0.1%SDS. Both 70% are homologous, approximately 50% of the structure and function of human proinsulin. The biological function of IGFs is achieved by binding to receptors on specific target cell surfaces. At present, two kinds of IGF receptors with different structures are found: IGF- I receptor and IGF- II receptor (mannose -6 phosphate receptor), also known as type I receptor, type II receptor. The former structure and insulin receptor (Insulin receptor Ir) is similar to that of 2 beta 2 glycoprotein four dimer consisting of alpha and beta two subunit alpha, alpha subunit is a ligand binding site, beta subunit with intrinsic tyrosine kinase activity and tyrosinase activity. IGF and insulin (Insulin, Ins) on IGF receptoraffinity of the order of Ir is Ins > > IGF- I IGF- II; on IGF- receptor: IGF- I IGF- II > > Ins; on IGF- II receptor: IGF- > IGF- I and Ins II, with no cross reaction.Unlike other growth factors, IGFs is associated with a specific binding protein (Binding, Proteins, BPs) in serum, in extracellular fluid and in cell cultures, and in the form of inactive complexes. So far, 6 IGFBP1, 2, 3, 4, 5 and 6 have been found, and their characteristic structures constitute a correlation. The secretory protein families are low molecular peptides, similar in structure to 50%. They are high affinity with two IGF without binding to insulin. In the blood and tissue fluid, the IGFBP3 content is highest, and more than 80% of the IGF in the cycle is combined with IGFBP3 to form the 150kDa three molecular complex (an unstable acid subunit, a binding subunit and IGF peptide). IGFBP2,5,6 has a higher affinity with IGF- II, and IGFBP1, 3, and 4 are similar in affinity to IGF- I and IGF- ii. IGFBP has the function of prolonging the circulating level of IGF half-life and stabilizing IGF serum concentration. Normally, the affinity of IGF with its binding protein is greater than or approximately equal to its receptor binding. In addition, the low expression of the high affinity receptor leads to a balance between a small amount of free IGF and a large number of IGF/IGFBP complexes. At present, there are at least three mechanisms involved in the activation of IGF:(1) parallel movement. In specific cases, such as growth, development, or damage to the organism, high affinity receptors are abundantly expressed, competing for IGF and separating it from binding proteins;(2) chemical modification of IGF or IGFBP, such as phosphorylation, to reduce the affinity of the complexes and dissociate them;(3) binding protein hydrolase specific water samples IGFBP to release the IGF.IGFs and growth and developmentIGF- I and IGF- II have similar structures and in vitro activity, but their biological effects are not the same. The biological functions of IGFs are not limited to mitogenic stimuli, but they can also induce differentiation or promote the expression of differentiated functions. The precise biological effects depend on the state of cell development and the presence of other hormones or growth factors. Especially in different tissues and different growth stages, there is a considerable difference in the function and level of IGF- I and IGF- ii. IGF- I, dependent on GH, can promote proliferation of many cells in vitro and promote protein and DNA synthesis. Many tissues and cells in the body can autocrine and paracrine IGF- I. IGF- II, known as the major growth factor before birth, does not require growth hormone regulation and is expressed in a variety of tissues and organs.Studies have shown that in early pregnancy, trophoblast cells invade the endometrium is strictly controlled by the micro environment; progesterone regulating endometrium and decidua and villus development and promote embryo implantation are mediated by IGFs, the mechanism was to increase the adhesion of the extracellular matrix, invasion and migration of humantrophoblast cells to stimulate, promote early embryo cultivation. In vitro experiment of Kniss and IGFs could promote early pregnancy decidua and villi on transport of glucose and amino acids, in a dose-dependent manner, suggesting that the fetal circulation before the embryo mainly from the surrounding environment and nutrition, through the role of IGFs. At the same time, a large number of studies have shown that during embryonic development, the level of IGF- II mRNA is much higher than that of IGF- I and mRNA, and has higher expression in embryonic tissues. With the increase of differentiation degree, the expression of it decreases. The expression of mRNA and IGF-I is affected by many factors, a large increase in liver, heart and kidney after birth than before birth; and significantly decreased in muscle, stomach and testis after birth than before birth; only IGF- in the brain and lung of mRNA showed a wavy change. Clinical studies have shown that the concentration of IGF- I in maternal circulation increases during pregnancy, and that fetal IGF- I is approximately 15 weeks pregnant. The levels of IGF-, I and IGFBP1 in umbilical artery and umbilical vein were similar. There was no significant difference between the two groups, indicating that the secretion of IGF- I in the mother and fetus was independent, and that IGF- I might not pass through the placenta. Some scholars detected the concentration of cord blood IGF- I, and the results showed that intrauterine fetal growth retardation, IGF- in cord blood was lower than that in gestational age group by about 40%, while that of gestational age IGF- was 8% to 10% higher than that in gestational age group. IGFBP1 increased significantly in preterm infants and small in gestational age infants, and negatively correlated with birth weight. There are serum levels and neonatal IGF- I reported the birth weight andlength were positively correlated, and as the main growth factor before the birth of IGF- II and the neonatal birth height and weight have no obvious correlation, and decreased rapidly after birth. Arsio IGF- concentration was measured in umbilical cord blood of 131 gestational age between 19 and 40 weeks of gestation by umbilical vascular puncture. The results showed that IGF- I was positively correlated with gestational age. In conclusion, the mechanism of IGFs's action on the fetus is not very clear, but its role in fetal growth and development has been widely recognized. This is also confirmed by genetic studies. Growth inhibition was first observed at 10.5 days after the mutation of IGF- I and IGF- II genes, and the weight of newborn rats at birth was only 30% of the normal weight of wild species. Another report: IGF- I and IGF- II deficient mice or IGF- II R and IGF- I R have defects in animal performance not only dwarf more serious, only 45% wild mice, these small animal have obvious muscle hypoplasia, the number of fiber cells in skeletal muscle and reduce serious skin hypoplasia. Births often die of respiratory failure. In conclusion, the expression of each of the IGF and IGF receptors is essential for normal embryo and fetal growth, and indicates that the two are absent and very few other components are up and down. Daughaday pointed out in 1988 that postnatal human plasma IGF- I and IGF- II concentration is inversely related to possible mechanisms for the competition between IGF-BP3 (1); (2) both inhibit the secretion of GH, and the GH of IGF- I IGF- II positive regulation; through the secretion of GH play a role of indirect inhibition of IGF-I. It can be assumed that it is precisely because of the interaction between IGF- I and IGF- II that the body's response is balanced. The process of growth and development of IGF- I was regulated by GH and other growthfactors. The expression level of IGF- I increased after birth was related to GH, and the tissue with decreased expression was related to specific factors. A large number of studies on the IGF- I and -GH axis have recently suggested that GH stimulates liver secretion of IGF- I, and IGF- I, in turn, inhibits GH. The complex of IGF and binding proteins in the cycle constitutes the major repository of IGF- I in circulation, and GH regulates its cycle levels. In the past, somatic cell theory suggested that most of GH's action was mediated by cyclic IGF- I during the linear growth of the organism,But recently, GH has been found to stimulate the production of IGF- I, a autocrine or paracrine action of IGF- I, which is important for normal growth in rodents, liver, and other tissues. Molecular biology studies were conducted using animal experiments to examine malnutrition in children due to inadequate caloric and protein intake. The results showed that malnutrition in children caused by growth arrest, the key is the diminutive of IGF- gene transcription level decreased, liver cell IGF- I decreased mRAN level, decrease of plasma IGF- content of clear, too fast. The mechanism of action may be the regulation of GH on the expression of IGF- I gene. Therefore, IGF- I is closely related to the growth and development of children.In addition, Urderwood reported the use of IGFs in the treatment of GH insensitive short stature patients, including Laron's syndrome and GH deficiency. Laron's patients lack GH receptors and do not respond to GH. Such patients have low levels of IGF- I, slow growth, but high levels of circulating GH, which is due to a decrease in GH feedback inhibition by IGF- I. The GHdeficient person mistakenly identified GH as an exotic protein, producing a large number of antibodies that weakened or disappeared the body's response to GH. One case of Laron's boys treated with GH showed no improvement in growth rate, but was treated with IGF- I for 2 years and grew at a rate of 10cm/ years. In addition, recent studies have shown that GH itself is not directly required for growth, and all the height development described by GH is actually done by IGF- I.The research of IGFs is a hotspot in the field of cell biology, and has been paid more and more attention to. It will probably become an important breakthrough for human beings to explore the mysteries of life. IGF is closely related to human embryo development and individual growth and development. However, the effect of IGF on many system tissues is only in vitro and animal experiments, so there is still much work needed to do further research on IGFs.ReferenceWH., Salmon, WD, Daughaday, A, hormonally, controlled, serum, factor, which, stimulates, sulfate, in, corporation, by,, cartilage, in, vitro., J,, Lab, Clin, Med, 1957,49:825-836.2 Froech ER. Antibody-suppressible and nosuppressible insulin-like acitivities in human serum and their physiologic significance. An insulin assay with adipose tissue of incneased precision and specificity. J Clin Invest, 1963,42:1816-1834.3 Pierson RW, Jr.The partial purification from calf serum ofa fraction with multiplication-stimulating activity forchicken firoblasts in cell culture and with non-suppressible insulin-like activity. J Cell Physiol, 1972,79:319-329., Grudice, IC.Insulin-like, factors, and, growth, ovarian, follicular, development.Endocrine, Reviews, 1992,13:641-665., Froesch, ER., of, insulin-like, Action, growth, factors., Ann, Rev, Physiol, 1985,47:443-467., Stylianopoulou, F.Pattern, of, the, insulin-like, growth, factor, II, gene, expression, during, rat, embryogenesis., Development, 1988103:497-506.Suface, Irving, JA, Lala, PK.Function, role, of, cell, integrins, on, human, trophoblast, cell, migration:regulation, by, TGF-beta,, IGF-, II, and, IGFBP1.Exp, Cell, Res, 1995217:419-427.The "Kniss DA.Insulin-like grouth factors:Their regulation of glucose and amino acid transport in placental trophoblasts isolated 1994,39:249-25. from first-trimester chorionic villi.J Report Med"9 Liu Baoying, Wang Li. Advances in the study of insulin growth factors. Foreign Medical Sciences, molecular biology section,.1996, 18:103-106.10 HS, Qu Xinzhong, Li Guilin. Effects of growth factors and hormones on the fetus. Foreign medical * maternal and Child Health Sciences, 1996, 7:162-163., Steven, D.The, growth, hormone/insulin-like, factor, axis, in, intrauterine, growth, growth, retardation:, Pathophysiological, and, therapeutic, implications., Endocrinology, 1996,6:294-300.,...12 children's longevity. Malnutrition molecular basis affect the children's growth: insulin-like growth factor gene expression in.Advances in Physiological Sciences, 1995, 26:144.1993,75:73-82., Julie, Baker, Liu, JP, Robertson, EJ, et, al.Role, of, insulin-like, growth, factors, in,, embryonic, and, postnatal, growth.Cell,...Perkins, Liu, JP, Baker, J, AS, et, al., Mice, carrying, null, mutations, of, the, genes, encoding, insulin-like, growth,, factor, I, and, the, typy,,, IGF, receptor.Cell,1993,75:59-72.15 Plilippe F, Backel Jauw. Louis E, Underwood et al. Prolonged treatment with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome-A clinical research center study.J Clin Endocrinology and Metab.1996,8: 3312-3314.Shanghai Ya Xi (International) snow America authorized biomedical technology services center marketing P Department。
IGF1重组人胰岛素样生长因子-1解决方案胰岛素样生长因子-1 是一种多功能细胞增殖调控因子,生物学功能主要是刺激细胞有丝分裂,诱导及促进细胞分化。
重组人胰岛素样生长因子-1(recombinant human insulin-like growth factor-1,rhIGF-1,1) 临床上主要用于治疗儿童原发性胰岛素样生长因子-1 严重缺乏导致的生长障碍和生长激素基因缺失且体内出现生长激素中和抗体患儿的生长不足,1还用于治疗胰岛素抵抗性糖尿病、神经损伤、骨质疏松、分解代谢等多种疾病。
参考资料:1.Title:Oestrogen-induced androgen insufficiency results in a reduction of proliferation and differentiation of spermatogonia in the zebrafish testis.Publication: Journal of Endocrinology (2009) 202, 287–297.Application: support spermatogenesis in an androgen-independent manner (Leal et al. 2006)2.Title:Suppression of Anoikis by SKP2 Amplification and Overexpression Promotes Metastasis of Esophageal Squamous Cell Carcinoma .Publication:doi: 10.1158/1541-7786.MCR-08-0092 Mol Cancer Res January 2009 7; 123.Title:MECHANISMS OF BIOMATERIAL MEDIATED FIBROTIC RESPONSES AND STRATEGIES TO IMPROVE TISSUE REACTIONS TO BIOMATERIAL IMPLANTS.Publication:THE UNIVERSITY OF TEXAS AT ARLINGTONMay 20104. Title: Cancer-Associated Carbonic Anhydrases IX and XII: Effect of Growth Factors on Gene Expression in Human Cancer Cell Lines.Publication: Journal of Cancer Molecules 5(3): 73-78, 2010.ProSpec 是一家细胞因子蛋白生产和研发的公司,具有20多年的生产经验,专注于蛋白(重组及合成)生产研发。
胰岛素样生长因子与脑缺血魏俊杰;孙晓慧;唐德义【期刊名称】《山东医药》【年(卷),期】2005(45)19【摘要】胰岛素样生长因子(IGF)包括IGF-Ⅰ、IGF-Ⅱ及Des-IGF-Ⅰ,由70个氨基酸组成。
50%的氨基酸序列与胰岛素前体一样,含有A、B、C、D四个结构阈,是一类多肽类生长因子,存在于多种组织中,也存在于脑组织,是一类重要的调节神经生长及修复的生物活性物质。
近年研究发现,IGFs及其受体及IGFs结合蛋白参与脑缺血损伤的病理过程,脑缺血后IGFs及其受体在脑皮层及纹状体系统表达增加,是一类重要的神经生长因子,参与脑缺血后内源性的神经保护机制,是潜在的脑缺血缺氧的神经保护剂。
【总页数】2页(P85-86)【作者】魏俊杰;孙晓慧;唐德义【作者单位】诸城市人民医院,山东诸城,262200;诸城市人民医院,山东诸城,262200;诸城市人民医院,山东诸城,262200【正文语种】中文【中图分类】R743.34【相关文献】1.脂肪源性干细胞穴位注射对大鼠脑缺血再灌注后胰岛素样生长因子1及其受体表达的影响 [J], 李文媛;王莹;刘洋;佟晓杰2.胰岛素样生长因子1对局灶性脑缺血大鼠的神经功能及神经细胞凋亡的影响 [J], 马莉3.补肾活血与益气活血方药对脑缺血老龄大鼠白介素-1和胰岛素样生长因子的影响 [J], 周清安;李建生;王至婉;李小黎;侯秀娟4.胰岛素样生长因子-1基因修饰骨髓基质细胞对大鼠脑缺血的神经保护作用 [J], 支东一;李偲;吴岚;刘开祥;李浩5.miR-122对脑缺血再灌注损伤小鼠脑梗死体积及胰岛素样生长因子-1受体通路的影响 [J], 廖晓斌;刘子彪;吕志成;康承湘因版权原因,仅展示原文概要,查看原文内容请购买。
胰岛素样生长因子对细胞增殖的调控作用胰岛素样生长因子(insulin-like growth factor,IGF)是一种低分子量的多肽激素,与胰岛素结构相似,但功能不同。
胰岛素主要调节葡萄糖代谢,而IGF则主要调节细胞的生长、增殖和分化。
IGF包括IGF-1和IGF-2两种形式,IGF-1是最具生物学活性的一种。
IGF是Insulin(胰岛素)超家族成员,故被称作胰岛素样生长因子。
IGF-1是由肝细胞和其他组织合成的一种多肽激素,在胚胎发育、儿童生长和成人代谢和维持多种生理功能均起到重要作用。
在细胞生长和增殖方面,IGF-1通过与细胞表面上IGF-1受体结合,激活信号转导途径,从而促进细胞生长和增殖。
IGF-1不仅直接作用于细胞,还可以通过诱导其他生长因子的表达或激活,促进细胞的生长和增殖。
IGF-1对细胞的生长和增殖调控在许多生理和病理过程中都起到了重要作用。
例如,IGF-1促进胚胎和儿童生长,维持成人的代谢和健康;在癌症的发生和发展过程中,IGF-1也发挥了重要作用。
IGF-1在癌症中的作用IGF-1对癌症的促进作用已经得到了广泛研究和认识。
IGF-1可以激活多个信号转导通路,如PI3K/Akt、Raf/MEK/ERK和JAK/STAT等,从而促进肿瘤细胞的生长和增殖。
同时,IGF-1还可以抑制细胞凋亡和增强肿瘤细胞的侵袭和转移能力。
在许多类型的癌症中,IGF-1和IGF-1受体的表达量都明显升高。
例如,IGF-1和IGF-1受体在乳腺癌、前列腺癌、胃癌和结直肠癌等多种癌症中都被发现表达水平升高。
此外,IGF-1在肝癌、骨肉瘤和神经母细胞瘤等肿瘤中也表现出促进作用。
因此,IGF-1和IGF-1受体就成为了癌症治疗的重要靶点。
研究人员通过开发针对IGF-1受体的抗体、还原剂和小分子抑制剂等,试图抑制IGF-1在肿瘤中的作用,达到治疗癌症的目的。
IGF-1对干细胞的作用除了在癌症中的作用,IGF-1还对干细胞的生长和增殖起到了重要作用。
胰岛素样生长因子结合蛋白—1检测在胎膜早破中的应用摘要目的探讨胰岛素样生长因子结合蛋白-1(IGFBP-1)检测在胎膜早破中的应用效果。
方法91例胎膜早破孕妇设为A组,同期80例无胎膜早破孕妇设为B组。
对两组孕妇阴道分泌物进行胰岛素样生长因子结合蛋白-1检测、pH 试纸检测,对比分析两种检查方法的阴性预测值、阳性预测值、灵敏度、特异性。
结果A组胰岛素样生长因子结合蛋白-1检测阳性率高于pH试纸检测,B 组胰岛素样生长因子结合蛋白-1检测阳性率低于pH试纸检测,差异具有统计学意义(P<0.05)。
胰岛素样生长因子结合蛋白-1检测阴性预测值为96.30%,阳性预测值为97.78%,灵敏度为96.70%,特异性为97.50%,明显高于pH 试纸的71.74%、82.28%、71.42%、82.50%,差异均有统计学意义(P<0.05)。
结论通过检测阴道分泌物中的IGFBP-1 ,可以快速、准确地诊断胎膜早破的发生,且具有敏感度高、特异性好及操作简单等优点,值得临床推广应用。
关键词胰岛素样生长因子结合蛋白-1;阴道分泌物;胎膜早破在产科临床工作中胎膜早破是孕妇最常见并发症之一,据研究[1]统计显示,中国孕妇足月胎膜早破(孕期>37周)的发生率可达10 %。
胎膜早破的发生严重威胁着孕产妇及新生儿身体健康及生命安全,孕妇继发胎盘早剥、羊水栓塞、宫内感染以及产后产褥期感染机率明显增加,使得孕妇难产率和早产率及新生儿死亡率明显增高。
因此,及时正确地诊断,以及及时正确的处理治疗是防止胎膜早破孕妇和新生儿发生严重并发症的关键[2]。
本文探讨胰岛素样生长因子结合蛋白-1检测在胎膜早破中的应用效果,报告如下。
1 资料与方法1. 1 一般资料选取本院2014年1月~2015年9月91例胎膜早破孕妇设为A组,同期80例无胎膜早破孕妇设为B组。
均为单胎,年龄21~38岁,平均年龄(26.9±4.5)岁,孕周37~41周,平均孕周(38.4±1.8)周,孕次1~4次,平均孕次(2.4±0.6)次。
胰岛素样生长因子在儿童矮小症诊治中的价值摘要:目的:探讨胰岛素样生长因子-1(IGF-1)在儿童矮小症诊治中的应用价值。
方法:对2018年6月-2023年5月围场满族蒙古族自治县医院60例进行矮小症诊断的生长发育迟缓的儿童展开研究,根据诊断结果分为矮小组和正常组,对比两组儿童的胰岛素样生长因子(IGF-1)的水平、身高情况、血清生长激素(GH)水平。
结果:诊断出的矮小症儿童有31例,纳入矮小组,健康的儿童有29例,纳入正常组。
结果显示,矮小组儿童平均身高(111.23±5.43)cm,低于正常组的(131.65±5.62)cm,组间差异具有统计学意义(P<0.05);矮小组儿童平均IGF-1水平为(65.67±10.77)ng/mL,正常组儿童平均IGF-1水平为(142.66±12.67)ng/mL,组间差异具有统计学意义(P<0.05);GH对比,矮小症为(5.92±1.01)ug/L,正常组为(6.73±1.05)ug/L,组间差异具有统计学意义(P<0.05)。
结论:矮小症儿童胰岛素样生长因子(IGF-1)的水平较低,与GH和身高呈正比,可作为诊断矮小症的指标。
关键词:儿童矮小症;胰岛素样生长因子;临床诊断矮小症是儿童生长发育过程中最阻碍身高发育的疾病,其中特发性矮小症(ISS)是最常见的,矮小症儿童表现为身材矮小。
同时矮小症也会导致儿童出现自卑、内向的情绪,还会影响儿童成年后的择偶和正常工作[1]。
而在儿童生长期对矮小症进行尽早诊断和尽早治疗,对于促进儿童生长发育至关重要。
临床上采用的常规生长激素激发试验儿童往往难以接受,而胰岛素样生长因子(IGF-1)的水平与儿童生长发育密切相关,通过测定IGF-1水平可实现对儿童矮小症的诊断。
因此,本文通过对2018年6月-2023年5月围场满族蒙古族自治县医院接受矮小症诊断的60例生长发育迟缓的儿童的胰岛素样生长因子水平进行测定,探索胰岛素样生长因子在儿童矮小症患者诊断和治疗中的应用价值。
胰岛素样生长因子1对骨代谢调节的研究进展李琳1,李琪1,张林忠2 (1.山西医科大学麻醉学院,山西太原 030012;2.山西医科大学第二医院麻醉科,山西太原 030001) 胰岛素样生长因子 1(insulin likegrowthfactor 1,IGF 1)是一种活性蛋白多肽物质,具有舒张血管、促生长、创伤修复、促进骨合成代谢等多种生理功能。
IGF 1通过与成骨细胞、软骨细胞、破骨细胞及骨细胞的同源受体结合,引起一系列介导细胞增殖、迁移、分化和基因的激活,在骨代谢过程中发挥着重要作用[1]。
1 生物学性质1.1 结构特点 IGF 1属于胰岛素样生长因子(insulin likegrowthfactor,IGF)家族成员之一,其基因位于12号染色体上,包含6个外显子[2]。
其中,4、5、6号外显子选择性剪接产生3种mRNA亚型,即IGF 1Ea、IGF 1Eb和IGF 1Ec,信使RNA(messengerRNA,mRNA)翻译产生IGF 1前蛋白。
这些前蛋白羧基端延伸域的结构存在差异,Ea肽由IGF 1基因的4和6号外显子编码,Eb肽由4和5号外显子编码,Ec肽由4、5和6号的部分外显子编码。
Ec肽的产生是由于一个阅读框移位导致其羧基末端肽段序列与IGF 1Ea和Eb肽不同。
成熟的IGF 1被认为是该基因唯一具有生物活性的分子[3]。
IGF 1是由70个氨基酸通过3个二硫键交联组成的小肽段,分子量为7649Da[4]。
IGF 1的结构与胰岛素原有50%的同源性。
与胰岛素原类似,IGF 1被分为A、B、C和D四个结构域,A、B结构域都由2个域间二硫键和1个域内二硫键连接,并且都与C结构域连接;而C结构域在结构成熟过程中不会发生蛋白水解,这与胰岛素原不同。
IGF 1的1 29基因位点与胰岛素B链同源,42 62基因位点与胰岛素A链同源[5]。
1.2 产生及分布 IGF 1不仅是一种内分泌分子,在许多组织中也以旁分泌、自分泌的方式发挥作用。
胰岛素样生长因子重组类似物高效液相HPLC检测方案-IGF-1-胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)主要有肝脏合成、分泌,功能是调节人的生长发育,但近年来的研究发现在脊椎动物的许多组织、细胞中都存在IGF-1及IGF-1受体,这些细胞包括成纤维细胞,肌细胞,上皮细胞,内皮细胞,颗粒细胞,平滑肌细胞等。
2005年8月30日美国FDA通过Tercica公司的人源化美卡舍明注射剂(mecasermin,Tncrelex)是唯一重组人源化胰岛素样生长因子-1药物,为重组胰岛素样生长因子(rhIGF-1),该药物是目前被FDA批准的唯一用于儿童严重的原发性胰岛素样生长因子缺乏症(IGFD)长期治疗药物。
-LR3-IGF1-胰岛素样生长因子1重组类似物(LR3-IGF1)是一种胰岛素样生长因子1经过重组构建得到的。
LR3-IGF1与人IGF1有两点不同之处,一个是第三位的谷氨酸被精氨酸代替,第二个不同之处是在N端提供了多个13个氨基酸。
目前此重组类似物较多的应用在细胞培养中,临床主要作用与IGF-1一样,用于胰岛素抵抗的糖尿病的治疗,促进骨骼生长,还参与创伤愈合过程。
局部使用能促进受损坐骨神经的再生,还可以提高人体肌肉生成。
1、仪器与试剂1.1仪器、设备LC-10Tvp高效液相色谱仪Vertex 色谱柱:250mm×4.6mm×5μm振荡器针头过滤器微孔滤膜:0.45µm1.2试剂乙腈(HPLC)三氟乙酸(AR)纯水2、供试品溶液和对照品溶液的制备供试品溶液的制备样品经层析柱纯化后,收集,上机分析。
3、色谱条件色谱柱:C4, 4. 6 mmx250 mm,粒度5 µm流动相:以0.1%TFA:ACN=67:33波长:214nm流速:0.6mL/min4、测定法分别精密吸取对照品溶液和供试品溶液各10ul,注入液相色谱仪,测定,即得5、谱图。
igf-2分子量IGF-2是一种生物活性多肽,其分子量约为7.5 kDa。
IGF-2是一种重要的生长因子,对细胞增殖、分化和代谢具有重要调节作用。
本文将从IGF-2的功能、结构和调节机制等方面进行阐述。
IGF-2是胰岛素样生长因子(Insulin-like Growth Factor,IGF)家族的一员,由肝脏、肌肉、胰岛、肾脏等多个组织合成。
IGF-2通过与细胞表面的IGF受体结合,调控细胞的生长和分化。
IGF-2的受体主要包括胰岛素样生长因子受体(IGF-1R)和胰岛素样生长因子受体相关蛋白(IGF-2R)。
IGF-2与IGF-1R结合后,能够激活多种信号通路,如PI3K/Akt、MAPK/ERK等,从而促进细胞增殖和生长。
IGF-2的结构与胰岛素类似,包括A链、B链和C链。
其中A链和B 链通过两个二硫键连接在一起,形成二硫键桥。
C链的存在使IGF-2与胰岛素的结构有所不同。
IGF-2的结构决定了其与受体的结合方式和生物活性。
IGF-2通过与IGF-1R结合,激活下游信号通路,从而调节细胞的增殖和分化。
IGF-2的表达受到多种因素的调控。
在胚胎发育过程中,IGF-2的表达量较高,对胚胎生长和器官发育起着重要作用。
而在成年个体中,IGF-2的表达量较低,主要由遗传和表观遗传因素调控。
IGF-2基因的甲基化和组蛋白修饰等表观遗传机制对其表达起着重要作用。
此外,IGF-2的表达还受到环境因素和生理状态的影响。
IGF-2在生理和病理过程中发挥着重要的作用。
在胚胎发育中,IGF-2通过调节细胞增殖和分化,促进胚胎器官的发育。
在成年个体中,IGF-2参与维持组织和器官的正常生长和代谢。
IGF-2的异常表达与多种疾病的发生和发展密切相关。
例如,IGF-2过度表达与肿瘤的发生和进展有关。
IGF-2的异常表达还与胎儿生长受限、肥胖和糖尿病等疾病的发生有关。
为了更好地理解IGF-2的功能和调控机制,研究人员进行了大量的研究。
胰岛素样生长因子在牙周组织工程中作用的研究进展 【摘 要】目的:对胰岛素样生长因子在牙周组织工程中作用的研究进展进行综述。 方法:查阅近年来相关文献,分析总结胰岛素样生长因子在牙周组织工程的不同作用。结果:胰岛素样生长因子主要通过促进牙周膜细胞迁移、增殖、分化、促进分泌、血管再生等发挥作用。结论:胰岛素样生长因子在牙周组织工程中应用前景非常广泛,但还有一些问题问题需要解决。
据第三次全国口腔健康流行病学调查,我国65岁以上老人牙周病的发病率已达85.9%,也就是说每10个老人中就有至少8个人患牙周病。而牙体缺失的最常见原因也恰是牙周疾病导致的牙周组织缺失,此次调查结果也显示,65岁以上老人失牙率高达86.1%。这些都严重影响了人们的生活质量,如何才能通过治疗恢复或者再生牙周组织是口腔学者一直以来奋斗的目标,但是始终未能有实质性突破。牙周组织工程为学者提供了一个很好的研究平台。而牙周细胞又是许多学者选来作为牙周组织工程的种子细胞。
1 牙周膜细胞 牙周膜细胞(periodontal ligament cell, PDL ) 是具有多分化潜能的多能细胞,主要包括成纤维细胞、成骨细胞、成牙骨质细胞以及间充质细胞等多种细胞成分, 能再牙周环境中进行迁移、增殖、分化等活动, 能在牙根、牙龈等部位与结合上皮、牙龈上皮等组织附着, 分化形成具有牙周结构的组织, 在牙周组织再生中发挥着积极重要的作用[1][2]。
2 胰岛素样生长因子 胰岛素样生长因子分为IGF-I和IGF-II,分别由定位于12q23的基因和定位于11p15. 5的基因编码[3],他们由主要肝脏合成,通过内分泌、自分泌和旁分泌的方式进入血液循环系统[4],到达靶细胞后,他们分别与IGF-IR和IGF-IIR结合,然后通过丝裂原活性蛋白激酶(Ras/MAPK)和磷脂酰肌醇3激酶( P I3K/Akt)通路转导信号[5]。进而作用于细胞,促进其迁移、增值、分化等行为。体外培养细胞证明它通过促进DNA 复制和细胞增大而促进细胞增殖,还能诱导体外培养细胞分化[5]。近年来的研究发现, IGFs对牙周膜成纤维细胞、成牙本质细胞、成骨细胞等细胞有促进增殖、分化,胶原和基质的合成,增强ALP的活性等作用,因此其在牙周组织再生的研究中越来越受到人们的重视。
3 胰岛素样生长因子对牙周膜细胞的作用 3.1 胰岛素样生长因子对成纤维细胞的作用 IGF对成纤维细胞的作用主要体现在对成纤维细胞增殖和分泌的影响。在哺乳动物中, 细胞周期由G1 期进入S 期存在一个特殊的G1 / S 限制点。只有当细胞越过这个限制点才能进入S 期, 进而增殖,否则细胞将处于停滞状态[7]。Lovschall等的研究表明,胰岛素样生长因子在成纤维细胞增值分裂的G1期向S期转变 的过程中必不可缺[8],张绍昆等进一步研究显示, IGF-1作用于鼠成纤维细胞NIH3T3后, 导致细胞内限制点蛋白合成迅速增加。当细胞内限制点蛋白浓度迅速增加达到某一阈值, 细胞就通过限制点进入S 期。因此IGF-1 起到了促进成纤维细胞NIH3T3的分裂、增殖的作用[9]。章锦才等研究发现IGF能够促进牙周膜细胞合成蛋白和胶原纤维,其机理是IGF通过促进牙周膜细胞糖的分解而导致乳酸的蓄积,进而导致乳酸的浓度升高而降低了NAD+的水平,由于NAD+是PADPR合成的底物,NAD+水平下降则PADPR合成减少,同时IGF1还能通过降低PADPR合成酶的活性减少PADPR合成,而PADPR合成减少,可激活胶原基因的表达,致使胶原合成增加[10]。不仅如此,李玲等对rhIGF-Ⅰ微球对人牙周膜成纤维细胞作用的实验研究发现IGF还能增加非胶原蛋白纤维粘连蛋白(Fn)和碱性磷酸酶(ALP)的合成增加。刚开始空白对照组和rhIGF-Ⅰ-GMs 组人牙周膜成纤维细胞ALP 活性和合成Fn无显著性差异,但是第三天开始就出现了明显的差异。实验组的ALP的活性明显增强,Fn量也随之增多。由此可见IGF可增强人牙周膜成纤维细胞的ALP活性和促进Fn的合成。[11]。
3.2 胰岛素样生长因子对成骨细胞的作用 体外研究表明IGF在促进成骨细胞迁移、分化、增殖等方面有着十分重要的作用,能有效的增加成骨细胞数目, 增加骨胶原形成, 并最终促进骨基质形成。Mathonnet等通过应用IGF-I治疗研究表明,IGF-I可以抑制城成骨细胞凋亡,使其有丝分裂时间从48小时降至24小时,能够刺激成骨细胞DNA和RNA的合成 [12]。Hock JM等将一定浓度的IGF- 1加入胎鼠颅骨培养液中, 24h后发现, 骨前细胞增加了8 倍,成骨细胞数量增加了4倍多, 骨膜成纤维细胞数量增加了2倍多[13]。而国内实验发现不同浓度的IGF-1对成骨细胞有丝分裂均有增多,同时细胞培养的密度均增加,但是分布不均匀,王敏等采用第三代成骨细胞,将细胞浓度为3000个/ml的成骨细胞悬液,分别加入实验组IGF浓度为0.1,1,10ng/ml,对照组不加IGF,进行培养,结果发现传代细胞形态基本一致,细胞在培养液中开始呈圆形,2h后细胞贴壁,4-6h后,大部分细胞贴壁,形态以多角形为主。24h后,细胞完全贴壁。第2-3天,细胞增殖明显,核分裂相多见,以三角形、短梭形为主。4-5天,细胞长满瓶壁。通过MTT方法测定的OD值描绘细胞生长曲线,证明IGF-1在0.1-10ng/ml浓度范围内呈浓度依赖性增长[14]。而IGF-2又名骨骼生长因子,它不仅能够促进成骨细胞增殖,同时还能够促进并诱导成骨细胞合成Ⅰ型胶原及骨胶原,加速新骨的形成。除此之外,李彦等研究结果显示,向hPDLCs加入IGF-Ⅰ后ALP的活性都表现为显著增强的趋势,提示可以促进hPDLCs的成骨向分化,因为ALP作为一种膜结合蛋白,是牙周膜细胞中成骨细胞亚群的标志性蛋白,其ALP越高,表明细胞增殖越多[15]。所以IGF是骨生成的强刺激因子,能促进成骨细胞的骨形成作用,但是它还可促进破骨细胞的骨吸收作用。Nakao K等研究发现SGF(即IGF-2) 可上调破骨前体细胞周围微环境中的CXC 趋化配体7( CXCL7) 和间质源性因子1( SDF1) 的表达,增强了破骨细胞的增殖与分化,促使骨吸收,有利于骨骼改造[16]。
3.3 胰岛素样生长因子诱导间充质细胞向成牙本质细胞分化作用 间充质细胞是牙周膜中新生细胞的来源,扮演干细胞的角色,能够分化为成牙本质细胞等细胞;而成牙本质细胞是能够形成牙本质得细胞,在牙周组织工程有着十分特殊地位[17]。张光东等在实验中证实了IGF能够诱导间充质细胞在形态学和免疫学上向成牙本质细胞样细胞分化[18]。 为求进一步证实,谢家敏等通过《定向诱导人类牙乳头间充质细胞向成牙本质细胞分化》发现,IGF能够诱导人类牙乳头间充质细胞在细胞形态学、碱性磷酸酶活性、细胞免疫化学、人牙本质涎磷蛋白mRNA的表达上均具有成牙本质细胞的特性;细胞形态学上:加入IGF培养细胞呈现单一胞浆突起,胞核位于突起的 一侧,一些单极细胞呈现平行排列,形态上出现成牙本质样细胞改变,而空白对照组则未见胞浆突起;在碱性磷酸酶活性上:加入IGF培养细胞上清液中碱性磷酸酶活性均明显,和空白对照组相比有统计学意义(P < 0.01);细胞免疫化学上:加入IGF培养的部分细胞抗牙本质涎磷蛋白染色,细胞胞桨呈阳性着色,胞核无着色,见细胞呈单一胞浆突起,一些细胞的突起很长。空白对照组细胞未见阳性着色。人牙本质涎磷蛋白mRNA的表达上:加入IGF细胞经反转录- 聚合酶链反应后获得约599 bp 的特异性片段,表明两组细胞在mRNA 水平表达特异性牙本质涎磷蛋白。空白组未见表达,由此证明IGF能够诱导人类牙乳头间充质细胞向成牙本质细胞分化[19]。
结论 综上所述,可以确定胰岛素样生长因子在牙组织工程中有着十分广阔的应用前景,其作用主要表现在IGFs可以促进各种牙周膜细胞增殖,诱导牙周膜细胞分化,同时还能够促进牙周膜细胞分泌胶原和合成细胞基质的、增强ALP的活性等作用,还能促进颌骨成骨与骨骼的改建。同时随着近来不断对胰岛素样生长因子的深入研究,还发现IGF-1还可以通过激活P13K—Akt、MAPK和ERKl/2通路,刺激内皮细胞增殖,促进内皮细胞增值和移行,进而促进血管形成和增生,对牙周组织再生至关重要。但是目前如何更好的利用胰岛素样生长因子在牙周组织工程的研究进展中还有许多问题亟需解决,但最终相信通过众多学者的努力,克服困难,实现牙周组织再生目标[20]。
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