丝胶对2型糖尿病大鼠睾丸生长激素/胰岛素样生长因子-1轴的作用

目的 探讨丝胶对2型糖尿病大鼠睾丸生长激素（GH）/胰岛素样生长因子-1（IGF-1）轴的作用。 方法 40只雄性SD大鼠随机分为正常对照组、糖尿病模型组、丝胶治疗组和阳性对照组,每组均为10只。链脲佐菌素连续腹腔注射制作2型糖尿病大鼠模型,1周后以血糖≥16.7mmol/L作为成模标准。待模型成功建立后,模型组大鼠不做任何处理,丝胶治疗组大鼠给予丝胶灌胃［2.4g/(kg•d)］,阳性对照组大鼠给予二甲双胍［55.33mg/(kg•d)］灌胃,均为35d。采用酶联免疫吸附测定（ELISA）方法检测大鼠血清睾酮、GH和IGF-1水平;分别采用免疫组织化学染色、免疫印迹法和RT-PCR法检测睾丸GH、GH受体（GHR）和IGF-1的表达。 结果 丝胶可明显降低糖尿病大鼠血GH水平、下调睾丸GH的表达,升高血IGF-1和睾酮水平,上调睾丸IGF-1和GHR的表达（P＜0.05,P＜0.01）。并且丝胶治疗组各项指标与阳性对照组比较无明显差别（P＞0.05）。 结论 丝胶可通过调节糖尿病时GH/IGF-1轴紊乱改善生精功能,发挥对糖尿病生殖功能损害的保护作用,其作用与二甲双胍相当。     

丝胶对Ⅱ型糖尿病大鼠肝胰岛素受体和胰岛素受体底物-2的调控作用

目的:研究丝胶对Ⅱ型糖尿病大鼠肝细胞胰岛素受体(IR)及胰岛素受体底物-2 (IRS-2)表达的影响.方法:SD大鼠随机分为5组,分别为正常对照组、糖尿病模型组、丝胶治疗组、阳性对照组、丝胶预防组.采用链脲佐菌素连续腹腔注射法制作Ⅱ型糖尿病大鼠模型.丝胶治疗组大鼠给予丝胶(2.4g·kg-1·d-1)灌胃35 d,阳性对照组大鼠给予二甲双胍(55.33 mg·kg-1·d-1)灌胃35 d,丝胶预防组大鼠于2％链脲佐菌素(25 mg/kg)连续腹腔注射之前给予丝胶(2.4g·kg-1·d-1)灌胃35d.采用葡萄糖氧化酶法检测各组大鼠的空腹血糖;SP免疫组织化学显色、蛋白免疫印迹和RT-PCR检测肝细胞中IR和IRS2的表达.结果:丝胶可明显上调糖尿病大鼠肝胰岛素受体和胰岛素受体底物-2mRNA表达,显著增加IR和IRS-2蛋白的表达.结论:丝胶可通过上调糖尿病肝IR和IRS-2的表达,改善胰岛素抵抗,起到降低血糖的作用.     

生长激素、胰岛素样生长因子-Ⅰ与骨质疏松

生长激素（GH）和胰岛素样生长因子Ⅰ（IGF-Ⅰ）对于骨骼的生长发育以及维持骨量和骨密度具有十分重要的作用，GH与IGF-Ⅰ水平下降是导致骨质疏松的机制之一。动物实验和临床研究发现应用GH、IGF-Ⅰ可以改善骨密度、有利于促进骨折愈合，小剂量GH、IGF-Ⅰ治疗骨质疏松有很好的应用前景。本文综述了GH-IGF-Ⅰ轴与骨骼代谢的关系及其在骨质疏松治疗中的进展。     

丝胶对Ⅱ型糖尿病大鼠胰岛细胞的保护作用

目的:观察丝胶对Ⅱ型糖尿病大鼠胰岛细胞的保护作用.方法:SD大鼠随机分为正常组、模型组、丝胶组和二甲双胍组.模型组、丝胶组和二甲双胍组大鼠均建立链脲佐菌素致Ⅱ型糖尿病模型.待模型成功建立后,丝胶组和二甲双胍组大鼠分别给予丝胶和二甲双胍灌胃35d.分别检测各组大鼠的血糖;免疫印迹法检测各组大鼠胰腺Bax和Bcl-2蛋白、免疫组织化学显色观察各组大鼠胰岛细胞胰岛素和神经肽Y (NPY)蛋白的表达.结果:与模型大鼠相比,丝胶组和二甲双胍组大鼠的血糖、胰Bax和NPY蛋白的表达明显降低,Bcl-2和胰岛素蛋白的表达明显升高;且两组比较无明显差别.结论:丝胶对Ⅱ型糖尿病胰岛损伤具有保护作用;且作用与二甲双胍相当.     

姜黄素对糖尿病脑病大鼠海马IGF-1/IGF-1R表达的影响

目的观察姜黄素对糖尿病脑病大鼠胰岛素样生长因子1(IGF-1)、胰岛素样生长因子受体(IGF-1R)表达的影响,分析姜黄素的脑保护作用机制。方法实验动物分为4组:正常对照组(A组)、正常姜黄素组(B组)、糖尿病脑病组(C组)和姜黄素治疗组(D组)。以大鼠一次性腹腔注射链脲佐菌素(STZ)建立糖尿病脑病模型,姜黄素持续灌胃12周。观察大鼠的体质量、血糖、糖化血红蛋白变化,采用免疫组化、RT-PCR法检测IGF-1及IGF-1R表达的变化。结果与A组和B组大鼠相比,C组大鼠血糖、糖化血红蛋白明显增高,体质量下降,海马区IGF-1表达明显减少(P<0.05),同样海马神经元IGF-1R表达减少(P<0.05)。经姜黄素治疗后,D组大鼠糖化血红蛋白下降,体质量增加,血糖变化不大,海马神经元IGF-1表达增多(P<0.05),随之海马神经元IGF-1R表达增多(P<0.05)。结论大鼠海马IGF-1/IGF-1R表达的减少可能在糖尿病脑病发病机制中发挥着重要的作用,姜黄素有脑保护作用,其机制可能是通过调控IGF-1信号通路调节实现的。     

胰岛素样生长因子-1工程细胞在糖尿病中的治疗作用

目的 观察胰岛素样生长因子-1(hIGF-1)工程细胞移植对糖尿病模型鼠的降血糖作用.方法 将hIGF-1基因克隆入pAAV腺病毒相关病毒载体,以HEK293包装细胞及病毒颗粒,HT1080细胞检测病毒滴度.将高病毒滴度的病毒上清感染骨髓基质细胞(MSCs)并植入糖尿病模型小鼠腹腔内,观察病毒感染MSCs植入对糖尿病模型小鼠血糖的影响.结果 成功构建了hIGF-1腺病毒相关病毒载体,HEK293细胞包装得到了1012滴度的病毒上清.MSCs病毒感染率达60%.稳定表达hIGF-1的MSCs腹腔移植后,可见糖尿病小鼠的血糖明显下降(P＜0.05).结论 稳定表达hIGF-1的MSCs对糖尿病动物模型有降糖作用,说明IGF-1基因可作为糖尿病基因治疗的候选基因.     

胰岛素样生长因子-Ⅰ与胰岛素释放试验在糖尿病中的应用

探讨胰岛素样生长因子-Ⅰ(IGF-Ⅰ)与胰岛素(INS)释放试验结合应用对于了解不同类型糖尿病(DM)患者降糖功能受损情况及选择治疗方案、调整用药的作用。对67名正常人和217例DM患者行糖耐量试验(OGTT)、INS释放试验和IGF-Ⅰ测定的结果进行比较分析。空腹血糖与IGF-Ⅰ呈明显负相关，空腹INS与IGF-Ⅰ呈明显正相关。结论：对于人体内INS和IGF-Ⅰ两条降糖途径，INS释放试验能很好地反映前者的状况，IGF-Ⅰ能较好地反映后者的状况，两者结合分析对于DM的诊断和治疗有较大的价值。     

胰岛素样生长因子-1及其受体和结合蛋白-3与前列腺癌关系的研究进展

前列腺癌是老年男性最常见的泌尿系统恶性肿瘤之一,在欧美国家发病率占男性肿瘤第一位,死亡病因第二位,发病率随年龄增长而增高,平均每十年发病率增加2倍[1]。在我国,随着生活水平的提高、饮食结构的改变及人口逐渐老龄化，前列腺癌的发病率和死亡率亦在迅速增长。近年来有关胰岛素样生长因子-1及其受体和结合蛋白-3与前列腺癌的关系备受关注。本文就其与前列腺癌关系的研究进展作一综述。     

大鼠大脑中动脉闭塞后脑内胰岛素样生长因子-Ⅱ的表达

目的 探讨大脑中动脉闭塞(MCAO)后早期胰岛素样生长因子-Ⅱ(IGF-Ⅱ)在脑内的表达.方法 应用免疫组化方法检测SD大鼠MCAO后IGF-Ⅱ的表达.结果 免疫组化方法结果显示MCAO后再灌注12、24 h和72 h时,与假手术组相比,缺血侧大脑皮质IGF-Ⅱ免疫反应阳性细胞数表达均降低(12 h与24 h时P＜0.05,72 h时P＜0.01).结论 MCAO后早期缺血侧大脑皮质IGF-Ⅱ呈低水平表达,提示IGF-Ⅱ可能在脑缺血损伤中发挥一定作用.     

胰岛素样生长因子及胰岛素样生长因子结合结白-3与胎儿生长发育的关系

目的探讨胰岛素样生长因子-Ⅰ、胰岛素样生长因子-Ⅱ、胰岛素样生长因子结合蛋白-3与胎儿生长发育的关系,为FGR的临床诊断和治疗提供理论依据和新思路。方法分别采集确诊FGR组、正常对照组和巨大儿组胎儿脐血标本,采用放射免疫测定其中胰岛素样生长因子-Ⅰ、胰岛素样生长因子-Ⅱ、胰岛素样生长因子结合蛋白-3的含量。结果 1.FGR组脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平下降,巨大儿组脐血清IGF-Ⅰ水平升高;2.新生儿脐血清IGF-Ⅰ、IGF-Ⅱ水平与新生儿出生体重、身长、胎盘重量呈明显正相关关系,脐血清IGF-Ⅰ水平与胎龄呈明显正相关关系,脐血清IGFBP-3水平与胎龄、新生儿出生体重、身长、胎盘重量呈明显正相关关系;3.脐血清IGF-Ⅰ与IG-FBP-3水平与产妇产前体重呈明显正相关关系,IGF-Ⅱ水平与产妇产前体重呈正相关关系。结沦脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平可作为预测胎儿和胎盘生长发育情况的参考指标,IGF-Ⅰ水平是其中最灵敏的指标;脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平的降低可能是导致FGR的重要原因之一;监测产妇产前体重可以间接反映胎儿血IGFs及IG-FBP-3水平,进而反映胎儿的生长发育状况。     

The association of insulin-like growth factor-1 standard deviation score and height in Chinese children with type 1 diabetes mellitus

Assessing the relationship between IGF-1 and height in type 1 diabetes children. Seventy-two type 1 diabetes children and 190 controls were recruited. The height standard deviation score of type 1 diabetes children was significantly higher than controls. The height standard deviation score was higher than the target height standard deviation score in both type 1 diabetes and controls. Serum IGF-1 levels and the IGF-1 standard deviation score were significantly lower in type 1 diabetes patients compared with controls. There was a significant difference in IGF-1 standard deviation score between the good glycemic control group and control group. The height standard deviation score was significantly correlated with C-peptide and IGF-1 levels. Furthermore, the IGF-1 standard deviation score was significantly correlated with glycemic control and C-peptide. The growth hormone/IGF-1 axis is impaired in type 1 diabetes, but height with good or poor glycemic control is not impaired.     

丝胶对2型糖尿病大鼠海马蛋白激酶B信号转导通路的作用

目的探讨丝胶(彩色蚕茧经浸泡、水煎、浓缩获得)对2型糖尿病大鼠海马蛋白激酶B(Akt)信号转导通路的作用。方法 36只雄性SD大鼠随机分为3组(n=12):正常对照组、糖尿病模型组和丝胶治疗组。小剂量链脲佐菌素(25mg/kg)连续腹腔注射(1次/d,3d)建立2型糖尿病大鼠模型。丝胶治疗组大鼠给予丝胶灌胃[2.4g/(kg·d),35d]。TUNEL法检测海马CA1区神经元凋亡,Western blotting法和RT-PCR法检测海马Akt信号转导通路相关因子Akt、核转录因子kappa B(NF-κB)和前凋亡因子Bad蛋白和mRNA的表达。结果与正常对照组比较,糖尿病模型大鼠海马CA1区神经元的凋亡指数明显升高(P0.01);海马Akt、NF-κB的表达明显降低,Bad的表达明显升高(P0.01)。与糖尿病模型组比较,丝胶治疗组大鼠海马CA1区神经元的凋亡指数明显降低(P0.05);海马Akt、NF-κB的表达明显升高,Bad的表达明显降低(P0.01,P0.05)。结论丝胶可通过调节糖尿病模型大鼠海马Akt信号通路的异常变化减少海马神经元凋亡,对糖尿病海马损伤具有一定的拮抗作用。     

腺病毒介导hIGF-1基因转染对软骨细胞增殖的影响

目的：探讨腺病毒介导人胰岛素样生长因子(human insulin—like growth factor，hIGF-1)基因转染对软骨细胞增殖的影响。方法：构建携带hIGF—1基因的重组腺病毒并进行PCR、Western blot鉴定。体外培养人胚胎软骨细胞，用处于对数增长期的第3代软骨细胞进行实验?分别转染1、10、100及500不同感染复数单位(multiplicity of infection，MOI)的Ad／hIGF-1，用PBS做阴性对照，hIGF-1生长因子(100μg/L)做阳性对照，采用四氮甲基唑蓝(methyl thiazolyl tetmzolium，MTT)法检测不同时间、不同组别软骨细胞吸光度。结果：第2代重组腺病毒上清液中PCR鉴定含有hIGF-1基因，Westem blot，证实Ad／hIGF-1表达成熟的hIGF-1生长因子。不同病毒滴度转染对软骨细胞增殖的影响存在量效依赖关系，100MO1软骨细胞吸光度约为对照组3倍，1MOI与10MOI、500MOI对软骨细胞增殖的影响近似；PBS组随着细胞体外培养时间延长，细胞增殖下降，hlGF-1生长因子、hIGF-1基因对软骨细胞增殖的影响存在时效关系，72h达到峰值。结论：Ad／hlGF-1基因转染对软骨细胞增殖的影响存在量效、时效依赖关系。     

2型糖尿病与结直肠癌关系的研究进展

2型糖尿病患者易罹患结直肠癌，若接受胰岛素治疗，则不仅结直肠癌发病率更高，且肿瘤进展更加迅速。高胰岛素血症假说认为,异常增高的胰岛素及游离胰岛素样生长因子-1水平可促进结肠细胞增殖,最终导致结直肠癌的发生。由于结直肠癌可通过筛选试验得以早期发现,故建议2型糖尿病患者均应选择合适的筛选形式，特别是接受胰岛素治疗的患者应建议进行结肠镜检查，并且筛选间隔时间不得超过5年。     

胰岛素样生长因子-1对雪旺细胞氧化损伤的保护作用

目的:探讨胰岛素样生长因子-1(IGF-1)对雪旺细胞氧化损伤的保护作用。方法:用体外纯化培养的雪旺细胞建立氧化损伤模型,将培养细胞分成氧化损伤组、IGF-1保护组和正常对照组。四甲基偶氮唑蓝比色法(MTT)检测细胞的活性,生化技术检测细胞内超氧化物歧化酶(SOD)的含量,免疫印迹法检测凋亡蛋白Bcl-2的表达水平。结果:与对照组相比,H2O2处理组细胞胞体积缩小、空泡化,细胞活性降低,SOD含量明显减少,Bcl-2表达减弱;而IGF-1保护组细胞存活率明显升高,SOD含量较损伤组高,Bcl-2表达明显上调。结论:IGF-1对氧化损伤的雪旺细胞有保护作用。     

Expression of insulin-like growth factor 1 in sarcomas

The expression of insulin-like growth factor-1 (IGF-1) was studied in normal tissues, in eight benign lesions and in 50 sarcomas. In palmar fibromatosis the spindle cells in cell-dense areas exhibited a strong immunoreactivity. IGF-1 was variably found in leiomyosarcomas (7/8), malignant schwannomas (7/9), synovial sarcomas (2/3), liposarcomas (3/6), fibrosarcomas (1/3), malignant fibrous histiocytomas (10/18) and in one angiosarcoma. Two rhabdomyosarcomas failed to express IGF-1 and only the spindle cell component of synovial sarcomas was positive. Immunoreactivity for IGF-1 in 10 malignant filrous histiocytomas (MFH) appeared to be related to co-expression of smooth muscle actin. These findings imply that MFHs can be subdivided into a group of tumours which are devoid of morphological and immunophenotypic evidence of differentiation and a group which manifest immunophenotypic differentiation.     

转染hIGF-1基因增强兔退变椎间盘蛋白多糖的表达

目的 探讨人胰岛素样生长因子(hlGF-1)基因在退变椎间盘中的表达及对椎间盘中蛋白多糖(agglecan)的影响.方法 制备新西兰大白兔腰椎间盘退变(IDD)模型24只,随机分为Ad/CMV.hlGF-1、hlGF.1生长因子及PBS组,每组8只.IA-5、L5-6椎间盘中分别注射第2代Ad/CMV-hlGF-1(8×108PFU)、hlGF-1生长因子(100μg/L)、PBS均25μL.注射后1、2.4和8周,Western blot检测hlGF-1蛋白表达;RT-PCR检测aggrecan mRNA的表达.结果 hlGF-1蛋白带出现在7.6×103ku.Ad/CMV-hlGF-1组hIGF-I蛋白表达持续达4周以上,hIGF-1组表达持续约2周;PBS注射组无hIGF-1蛋白表达.aggrecan电泳条带出现在200～300 bp;在注射后1～4周,Ad/CMV-hlGF-I组内aggrecan mRNA相对表达量进行性增加,8周轻度下降,4个时期总的比较(F=8.51,P<0.05),注射后1～8周,hlGF-1组、PBS组aggrecan mRNA相对表达量进行性下降.结论 hlGF-1能够增强椎间盘aggrecan的表达.     

Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas

The insulin-like growth factor-1 receptor (IGF1-R) is a cellular receptor overexpressed in many tumor cell lines and in some human tumors that seems to play a critical role in transformation, tumorigenicity, and metastasis. To date, a comprehensive evaluation of tissue distribution of IGF1-R in human carcinomas from different anatomical sites has been lacking. Using stage-oriented human cancer tissue microarrays, we studied IGF1-R expression and distribution in a group of 152 human carcinomas from a variety of anatomical sites and from 63 normal tissues through immunohistochemistry. The tumors included carcinomas from breast (8), ovary (9), endometrium (7), esophagus (5), stomach (7), pancreas (7), liver (4), colon (10), kidney (14), bladder (17), prostate (11), head and neck (31), salivary glands (8), lung (13), and skin (1). Formalin-fixed, paraffin embedded tissues of each case were immuno-stained using the avidin-biotin peroxidase method and an anti-IGF1-R rabbit polyclonal antibody. High-membranous IGF1-R staining was observed in 7 of 8 (87.5%) breast carcinomas, in 9 of 9 (100%) ovarian carcinomas, in 7 of 7 (100%) endometrial carcinomas, in 5 of 7 (71.1%) gastric carcinomas, in 4 of 7 (57.1%) pancreatic carcinomas, in 9 of 10 (90%) colon adenocarcinomas, in 11 of 13 (84.6%) lung carcinomas, in 6 of 11 (54.5%) prostatic adenocarcinomas, and in 17 of 17 (100%) transitional cell carcinomas of the bladder. Only a minority of squamous cell carcinomas of the head and neck and esophagus (34), salivary gland tumors (5), and renal cell carcinomas (14) were IGF1-R positive. This study demonstrates the overexpression of IGF1-R across a wide variety of human carcinomas of glandular or transitional cell origin.     

The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing

Research studies clearly indicate that age‐related changes in cellular and tissue function are linked to decreases in the anabolic hormones, growth hormone and insulin‐like growth factor (IGF)‐1. Although there has been extensive research on the effects of these hormones on bone and muscle mass, their effect on cerebrovascular and brain ageing has received little attention. We have also observed that in response to moderate calorie restriction (a treatment that increases mean and maximal lifespan by 30–40%), age‐related decreases in growth hormone secretion are ameliorated (despite a decline in plasma levels of IGF‐1) suggesting that some of the effects of calorie restriction are mediated by modifying the regulation of the growth hormone/IGF‐1 axis. Recently, we have observed that microvascular density on the surface of the brain decreases with age and that these vascular changes are ameliorated by moderate calorie restriction. Analysis of cerebral blood flow paralleled the changes in vasculature in both groups. Administration of growth hormone for 28 d was also found to increase microvascular density in aged animals and further analysis indicated that the cerebral vasculature is an important paracrine source of IGF‐1 for the brain. In subsequent studies, administration of GHRH (to increase endogenous release of growth hormone) or direct administration of IGF‐1 was shown to reverse the age‐related decline in spatial working and reference memory. Similarly, antagonism of IGF‐1 action in the brains of young animals impaired both learning and reference memory. Investigation of the mechanisms of action of IGF‐1 suggested that this hormone regulates age‐related alterations in NMDA receptor subtypes (e.g. NMDAR2A and R2B). The beneficial role of growth hormone and IGF‐1 in ameliorating vascular and brain ageing are counterbalanced by their well‐recognised roles in age‐related pathogenesis. Although research in this area is still evolving, our results suggest that decreases in growth hormone and IGF‐1 with age have both beneficial and deleterious effects. Furthermore, part of the actions of moderate calorie restriction on tissue function and lifespan may be mediated through alterations in the growth hormone/IGF‐1 axis.