IGF-I和IGF-IR在高氧致新生鼠慢性肺疾病中的动态表达及其作用

目的研究IGF-I、IGF-IR在高氧致新生鼠慢性肺疾病（CLD）中的表达及作用。方法将足月新生大鼠144只随机分为高氧组和空气组,分别于实验1d,3d,7d,10d,14d,21d应用免疫组化和RT-PCR技术检测IGF-I、IGF-IR的动态表达。结果CLD时IGF-I和IGF-IR呈动态变化,高氧组和空气组比较,在实验3d～10d IGF-I和IGF-IR表达明显降低（P〈0.05）,14d和21d表达明显增强（P〈0.05）。结论IGF-I和IGF-IR是肺泡发育的正向调节因子,与CLD时肺泡分隔受阻、肺泡成熟障碍和肺纤维化有关。     

胰岛素样生长因子-Ⅰ与乳腺癌

胰岛素样生长因子Ⅰ(insulinlikegrowthfactor,IGF)对细胞增殖和凋亡具有双重调节功能。在临床上,它的异常伴随着多种慢性疾病或肿瘤倾向;在乳腺癌的发生发展过程中,其作用也异常重要。深入研究其功能及相关影响因素,将为临床乳腺癌的诊疗提供新思路和新办法。     

胰岛素样生长因子-Ⅰ对人肾小管上皮细胞转分化及胶原合成的作用

目的探讨胰岛素样生长因子-Ⅰ(IGF-Ⅰ)在人肾小管上皮细胞转分化及胶原合成中的作用。方法将体外培养的人肾小管上皮细胞HK2分为2组(1)对照组;(2)IGF-Ⅰ组培养液中加入终浓度分别为25、50、100、200μg/L的IGF-Ⅰ。用倒置显微镜观察细胞形态变化,以RT-PCR检测HK2细胞α-平滑肌肌动蛋白(α-SMA)、胶原Ⅰα和胶原ⅢαmRNA表达的变化。ELISA方法检测培养上清中胶原Ⅰ的浓度。结果IGF-Ⅰ刺激使HK2细胞由椭圆形变为梭形。不同浓度的IGF-Ⅰ作用于HK2细胞48h后,α-SMA、胶原Ⅰα和胶原ⅢαmRNA水平显著升高(P<0.05);ELISA结果显示,100及200μg/LIGF-Ⅰ组中HK2细胞分泌的胶原Ⅰ显著增加(P<0.05)。结论IGF-Ⅰ在体外能够诱导人肾小管上皮细胞转分化,并促进其胶原的合成。     

胰岛素样生长因子Ⅰ研究进展

本文介绍胰岛素样生长因子（ＩＧＦ－Ⅰ）的结构和生理作用及其在糖尿病治疗方面的应用。因ＩＧＦ－Ⅰ的降血糖作用可通过ＩＧＦ－Ⅰ受体介导，故对胰岛素受体缺陷和胰岛素抵抗患者可尝试应用，但长期使用的安全性和有效性尚需进一步研究。     

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。     

胰岛素样生长因子Ⅰ、胰岛素样生长因子Ⅰ受体在大肠癌中的表达及其意义

目的检测胰岛素样生长因子Ⅰ（IGF-Ⅰ）、胰岛素样生长因子Ⅰ受体（IGF-ⅠR）蛋白在大肠癌中的表达,并分析与临床病理学因素的关系．探讨两者在大肠癌发病机制中的相互作用及与患者预后的关系。方法选取不同类型的大肠癌组织48例（试验组）,其中男性25例,女性23例：年龄34～78岁,平均年龄53岁。任意选癌旁5cm以上的正常组织24例（正常对照组）。采用SABC法检测IGF-Ⅰ、IGF-ⅠR的表达。结果在48例大肠癌组织中,IGF-Ⅰ、IGF-ⅠR的阳性表达率分别为64．58％、58．33％,均显著高于癌旁正常组织中的16．67％、16．67％。IGF-Ⅰ、IGF-ⅠR在大肠癌组织中的表达与肿瘤的浸润程度、淋巴结转移、Dukes’分期有关。而与其他的病理因素及患者5年生存情况无关。IGF-Ⅰ和IGF-ⅠR在大肠癌组织中的表达呈明显相关性。结论IGF-Ⅰ、IGF-ⅠR可能相互协同作用参与大肠癌的浸润、转移,可作为反映大肠癌进展的重要生物学指标．但IGF-Ⅰ、IGF-ⅠR阳性表达与大肠癌患者的预后无明显相关性。     

胰岛素样生长因子-Ⅰ对肝硬变患者骨代谢的影响

为研究胰岛素样生长因子-Ⅰ(IGF-Ⅰ)对肝硬变患者骨代谢的影响,将44例肝硬变患者,按Child-pugh分级分为A、B、C三组,并用38名健康者作为对照组,分别测定血清IGF-Ⅰ、骨钙素(BGP)和右跟骨骨密度(BMD)值。结果表明,B、C组肝硬变患者IGF-Ⅰ、BGP和BMD较对照组明显降低(P<0.001),肝硬变越严重,IGF-Ⅰ、BGP、BMD降低越明显。IGF-Ⅰ分别与BGP、BMD呈正相关(r=0.398,0.357,P<0.05)。IGF-Ⅰ减少可能是肝硬变患者骨质疏松形成的重要原因。     

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。     

正常及糖尿病鼠眼胰岛素样生长因子Ⅰ基因表达的研究

用原位杂交，点杂交及Ｎｏｒｔｈｅｒｎ杂交技术研究了正常及糖尿病大鼠眼组织的胰岛素样生长因子Ⅰ基因。ＩＧＦ－Ｉ基因在眼组织的表达呈区域性，视网膜内核层及神经节细胞表达最强；脉络蟆，视网膜色素上皮细胞及外核层次之；巩膜最弱；角膜，晶体未见表达信号。糖尿病眼组织ＩＧＦ－Ｉ基因表达显著增强。     

胰岛素-胰岛素样生长因子-Ⅰ与胎儿宫内生长发育的关系

目的探讨母血、脐血中胰岛素-胰岛素样生长因子的水平-Ⅰ与胎儿宫内生长发育的关系及意义。方法收集2010年9月～2011年3月在本院分娩的单胎足月正常妊娠(无产科并发症)孕妇及其新生儿各90例,分娩前抽取孕妇空腹静脉血5 ml,胎儿娩出后即抽脐静脉血5 ml,标本收集后用高效液相色谱法测定母血、脐血中胰岛素及胰岛素样生长因子-Ⅰ的水平。结果 SGA脐带血清胰岛素、胰岛素样生长因子-Ⅰ水平明显低于AGA、LGA;AGA脐血胰岛素、胰岛素样生长因子-Ⅰ水平低于LGA组,差异均有统计学意义;母血胰岛素样生长因子-Ⅰ水平在SGA、AGA、LGA三组中差异有显著性(P<0.01),而胰岛素水平在SGA、AGA、LGA三组中差异无显著性;脐血中胰岛素与胰岛素样生长因子-Ⅰ水平呈正相关关系;脐血胰岛素、胰岛素样生长因子-Ⅰ水平与新生儿出生体重、身长、胎盘重量、体重指数呈明显正相关关系。结论脐血胰岛素、胰岛素样生长因子-Ⅰ水平与胎儿生长发育相关,低脐血胰岛素、胰岛素样生长因子-Ⅰ水平与胎儿宫内生长受限关系更为密切,母血胰岛素样生长因子-Ⅰ水平可作为评估胎儿宫内生长发育的指标。     

角化生长因子在慢性肺疾病早产大鼠的表达

目的探讨高氧致CLD早产大鼠KGF表达的变化规律.方法 60只新生早产大鼠随机分为2组,每组30只:A组-对照组;B组-高氧组(吸入95%O2).分别采用Western Blotting及RT-PCR检测肺组织KGF及其mRNA表达.结果高氧组肺内KGF及其mRNA表达高于对照组.结论高氧引起新生早产大鼠肺内KGF及其mRNA的表达随时间发生变化.     

Role of insulin-like growth factor I signaling in neurodegenerative diseases

Disturbed trophic support to neurons has long been considered a potential mechanism in neurodegeneration. Recent evidence indicates that intracellular trophic signaling may be compromised in several neurodegenerative diseases. Changes in the levels of insulin-like growth factor I (IGF-I), a trophic hormone with multiple neuroprotective actions, have recently been observed in several human neurodegenerative illnesses. Therefore analysis of IGF-I pathways could help provide greater insight into trophic disturbances to neurons. However, neurodegenerative diseases with similar clinical manifestations show either high or low levels of circulating IGF-I. This apparently puzzling observation can be explained if we consider that IGF-I input to target neurons is disrupted by either lower IGF-I availability or by reduced cell sensitivity to IGF-I. The latter disturbance may be associated with high IGF-I levels. We hypothesize that in the majority of neurodegenerative diseases compromised IGF-I support to neurons emerges as part of the pathological cascade during the degenerative process and contributes to neuronal demise. In addition, loss of IGF-I input to specific neuronal populations might be the cause of a small group of neurodegenerative diseases.Abbreviations AT Ataxia-telangectasia - A Amyloid- - IGF Insulin-like growth factor - IGFBP Insulin-like growth factors binding protein - IRS Insulin receptor substrate protein - LID Liver IGF-1 deficiency - SCA Spinocerebellar ataxia - TNF Tumor necrosis factor     

Altered expression of type I insulin-like growth factor receptor in Crohn's disease

The fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal stricturing and in the maintenance of inflammation in Crohn's disease (CD). We aimed to describe IGF-1R expression in CD intestinal lesions, to compare it to other intestinal inflammatory diseases and to correlate it with fibrosis and apoptosis. IGF-1R expression and apoptosis (active caspase-3) were studied by immunohistochemistry. Surgical intestinal specimens [17 CD, nine controls, six diverticulitis and four ulcerative colitis (UC)] were used. IGF-1R was expressed transmurally mainly by inflammatory cells (IC) and smooth muscle cells, both in diseased intestine and controls. IGF-1R positive IC were increased in the mucosa and the submucosa of CD (P < 0.007), and in involved areas compared to uninvolved areas (P = 0.03). In UC, the number of IGF-1R positive IC was only increased in the mucosa, and was not different from controls in the submucosa. In diverticulitis, the number of IGF-1R positive IC did not differ from controls. In CD submucosa, IGF-1R expression in IC was inversely correlated with apoptosis in uninvolved areas (P = 0.01). Expression of IGF-1R in submucosal fibroblast-like cells, subserosal adipocytes and hypertrophic nervous plexi was specific for CD. We have shown a transmural altered expression of IGF-1R in CD. This may suggest a role for IGF-1R in the maintenance of chronic inflammation and stricture formation in CD.     

宫内发育迟缓大鼠血清胰岛素样生长因子Ⅰ、Ⅱ、BP3的变化及L-精氨酸的保护作用

目的通过L-精氨酸孕期干预后大鼠血清胰岛素样生长因子-Ⅰ、Ⅱ及结合蛋白3水平的变化,探讨L-精氨酸的保护作用及其机制。方法采用被动吸烟法造大鼠IUGR模型,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,测量胎鼠体重。应用酶联免疫吸附法检测各组大鼠血清IGF-Ⅰ、IGF-Ⅱ及IG-FBP-3水平。结果对照组、模型组与小、大剂量L-精氨酸防治组IUGR发生率分别为3.92%,54.95%,5.55%和9.09%。模型组大鼠血清IGF-Ⅰ、IGF-Ⅱ水平较对照组明显降低(P<0.01),小剂量和大剂量L-精氨酸防治组与模型组相比,IGF-Ⅰ、IGF-Ⅱ水平明显增高(P<0.01)。模型组大鼠血清IGFBP-3水平较对照组明显增高(P<0.01),小剂量和大剂量L-精氨酸防治组与模型组相比,IGFBP-3水平明显降低(P<0.01),与对照组亦有明显差异(P<0.01)。结论L-精氨酸可增高被动吸烟致宫内发育迟缓大鼠血清胰岛素样生长因子-Ⅰ、Ⅱ的水平,降低胰岛素样生长因子结合蛋白3的水平,从而促进胎鼠发育,防治IUGR的发生。     

肝素对鼠肺成纤维细胞胶原mRNA表达的影响

目的：探讨不同剂量的肝素对胎鼠肺成纤维细胞（LFb)了Ⅰ、Ⅲ型胶原mRNA表达的影响。方法：采用Northern印迹杂交方法检测Ⅰ、Ⅲ型胶原mRNA的表达。结果：浓度为0．1mg/L,1mg/L,10mg/L的肝素对Ⅰ、Ⅲ型胶原mRNA的表达的影响不明显：100mg/L的肝素则抑制Ⅰ、Ⅲ型胶原mRNA的表达。结论：Ⅰ、Ⅲ型胶原mRNA的表达与肝素剂量有一定的关系。     

重组人截短型胰岛素样生长因子1在大肠杆菌中的高效表达

目的：建立人截短型胰岛素生长因子１的原核高效表达系统。方法：利用基因重组技术将人人截短胰岛素样生长因子１「Ｄｅｓ（１－３）ＩＧＦ１」的ｃＤＮＡ片段克隆到融合蛋白表达载体ｐＭＴＹ４中,用离子交换层析法纯化蛋白并经ＳＤＳ聚丙烯酰胺凝胶电泳,放射免疫检测,Ｎ－末端前１６位氨基酸序列测定及生物活性检测等方法对所获蛋白进行了鉴定。结果;获得含人Ｄｅｓ（１－３）ＩＧＦ１基因的重组质粒,在大肠杆菌中高效表达出含     

大肠癌中胰岛素样生长因子2基因的印迹状态和表达

目的：研究胰岛素样生长因子2（insulin-like growth factor 2,IGF2)基因的印迹状态和表达与大肠癌的关系，为研究大肠癌的发生机理提供线索。方法：用逆转录－聚合酶链反应半定量检测IGF2的表达量，比较其在大肠癌及癌旁组织中有无差异，用限制性片段长度多态检测IGF2的印迹状态，分析印迹状态、表达量与大肠癌的关系。结果：82．4％（28／34）大肠癌有IGF2的表达增加，IGF2的表达量在肿瘤组织与癌旁组织中差异有显著性（P＜0．01，t=3.01)。IGF2在87．5％（14／16）大肠癌组织中发生了印迹丢失，但其相对应的癌旁组织也有71．4％（10／14）存在IGF2的印迹丢失。结论：IGF2的表达增加是大肠癌发生的相关因素，IGF2的印迹丢失可能是大肠癌发生的前期表现。     

Prognostic role of insulin‐like growth factor receptor‐1 expression in small cell lung cancer

Chang MH, Lee J, Han J, Park YH, Ahn JS, Park K, Ahn M‐J. Prognostic role of insulin‐like growth factor receptor‐1 expression in small cell lung cancer. APMIS 2009; 117: 861–9. Insulin‐like growth factor receptor‐1 (IGFR‐1) is a cellular membrane receptor which is overexpressed in many tumors and seems to play a critical role in anti‐apoptosis. The insulin‐like growth factor binding protein‐3 (IGFBP‐3) is known as a growth suppressor in multiple signaling pathways. The aim of this study was to determine IGFR‐1 and IGFBP‐3 expression in small‐cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. We analyzed IGFR‐1 and IGFBP‐3 expression in 194 SCLC tissues by immunohistochemical staining. Correlative analyses between IGFR‐1 and IGFBP‐3 expression in SCLC and clinicopathologic factors were performed. A total of 117 patients had extensive disease (ED) (60.3%) and 77 had limited disease (39.7%). With the median follow‐up duration of 49.5 months (24–82 months), the median progression‐free survival (PFS) and overall survival (OS) were 7.2 months [95% confidence interval (CI): 6.4–8.0 months] and 14.4 months (95% CI: 12.7–16 months), respectively. IGFR‐1 expression was observed in 154 of the 190 tumor tissues, whereas there was no IGFBP‐3 expression. Multivariate analysis showed that stage (p < 0.001), response rate (p < 0.001), and lactate dehydrogenase (LDH) levels (p < 0.001) were the independent prognostic factors for PFS, and age (p = 0.014), LDH level (p < 0.001), and stage (p < 0.001) for OS. The IGFR‐1 positivity was not associated with PFS or OS in the entire cohort. Subgroup analysis revealed that OS was significantly longer in patients with IGFR‐1‐positive tissue than IGFR‐1‐negative tissue in SCLC‐ED (p = 0.034). These results suggest that IGFR‐1 expression may be useful as a prognostic marker in patients with SCLC‐ED.     

RNA干扰沉默IGF—IR基因治疗卵巢癌的实验研究

目的研究RNA干扰技术沉默IGF—IR在卵巢癌靶向治疗中的意义。方法以IGF—IR为目的基因,设计合成siRNA重组质粒;利用Real—timePCR和Westernblot方法,分别从mRNA水平及蛋白水平检测IGF—IR的表达;通过MTF实验检测细胞增殖情况。结果本实验成功构建了三个表达载体pSihIGF—IR-1、pSihIGF—IR-2和pSihIGF—IR-3,转染卵巢癌OVCAR3细胞,48h后,IGF—IR的mRNA及蛋白水平均明显降低,并且显著抑制了OVCAR3细胞的体外增殖。结论应用RNA干扰技术,能够高效、特异的沉默IGF—IR基因的表达,抑制肿瘤生长。针对卵巢癌IGF—IR的RNAi技术,可能为卵巢癌的临床治疗开拓-条新的途径。