肺癌患者胰岛素样生长因子1和胰岛素样生长因子结合蛋白3的表达及其临床意义

目的 分析肺癌患者血清和支气管肺泡灌洗液（BALF）中胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）的表达,探讨其在肺癌诊断和预后中的临床意义.方法 运用免疫放射法检测80例非小细胞肺癌患者和14名健康者（对照组）外周血血清与BALF中IGF-1、IGFBP-3的水平.结果 肺癌组血清和BALF中IGF-1表达显著高于对照组（P＜0.01）,IGFBP-3的表达显著低于对照组（P＜0.05）,同时IGF-1/IGFBP-3升高（P＜0.01）.IGF-1、IGF-1/IGFBP-3在有淋巴结转移、远处转移和TNMⅢ～Ⅳ的肺癌患者血清、BALF中明显高于无转移者和TNMⅠ～Ⅱ期者（P＜0.05）,而IGFBP3下降明显高于无转移者及TNMⅠ～Ⅱ期者（P＜0.05）.肺癌组血清IGF-1、IGFBP-3浓度与BALF中的浓度呈正相关（P ＜0.01）;患者血清BALF中IGF-1与IGFBP-3浓度呈负相关（P＜0.05）.结论 非小细胞肺癌患者血清和支气管肺泡灌洗液中IGF-1、IGFBP-3的表达对肺癌的诊断、判断预后有重要临床意义.     

非霍奇金淋巴瘤患者血清胰岛素样生长因子-1及其结合蛋白-3表达水平的初步观察

目的:探讨非霍奇金淋巴瘤(NHL)患者血清胰岛素样生长因子-1(IGF-1)及其结合蛋白-3(IGFBP-3)表达水平及其临床意义.方法:选择28例诊断初发NHL患者(淋巴瘤组)及28例健康志愿者(对照组),化学发光法测定血清IGF-1及IGFBP-3水平并计算IGF- 1/IGFBP-3值,分析组间的差异.结果:血清IGF-1及IGFBP-3水平淋巴瘤组显著低于正常对照组(均P＜0.01);IGF-1/IGFBP-3淋巴瘤组与正常对照组差异无统计学意义(P＞0.05);不同亚型的淋巴瘤组的血清IGF-1、IGFBP-3水平及IGF-1/IGFBP-3比值的差异均未达到统计学意义(P＞0.05).结论:N HL患者血清IGF-I及IGFBP-3水平明显降低,可能与NHL相关.IGF-1/IGFBP-3比值与NHL无明显相关性,IGF-1及IGFBP-3水平与NHL的分型无明显相关.     

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.     

结直肠腺瘤患者血清IGF-1和IGFBP-3的变化及其临床意义

目的:研究血清胰岛素样生长因子1(insulin-like growth factor1,IGF-1)和胰岛素样生长因子结合蛋白3(insulin-like growth factor binding protein3,IGFBP-3)在结直肠腺瘤患者中的变化及临床意义.方法:采用放射免疫法和免疫放射法分别检测120例结直肠腺瘤患者、48例结直肠癌患者及34例健康人外周血清IGF-1和IGFBP-3表达水平.结果:血清IGF-1和IGF-1/IGFBP-3比值在结直肠癌组(247.35±60.77;0.063±0.010)、腺瘤性息肉组(224.75±69.45;0.055±0.010)及健康对照组(195.39±63.37;0.047±0.013)依次降低,前两组明显高于后组,差异有统计学意义(P<0.05).腺瘤性息肉患者血清IGF-1、IGFBP-3水平及IGF-1/IGFBP-3比值与患者的性别、年龄、吸烟饮酒情况及肿瘤家族史临床指标间均无统计学意义;与息肉大小、数量、部位、组织学分类也无统计学意义.血清IGF-1和IGF1/IGFBP-3比值在结直肠癌组(247.35±60.77;0.063±0.010)、进展期腺瘤组(235.81±73.72;0.056±0.011)及早期腺瘤组(208.15±59.44;0.052±0.008)依次降低,且前两组较后组比,差异有显著性(P<0.05).结直肠腺瘤性息肉患者血清IGF-1和IGFBP-3呈正相关(r=0.796,P<0.001).结论:血清IGF-1和IGF-1/IGFBP-3比值增高可能在结直肠腺瘤癌变中起一定作用,对适龄人群行血清GF-1和IGF-1/IGFBP-3检测可以简单筛选有息肉恶变倾向者.     

水甘油通道蛋白9短发夹RNA的构建与筛选及其对非酒精性脂肪性肝病细胞模型的作用

目的 构建人水甘油通道蛋白9 (AQP9)短发夹RNA (shRNA),筛选出沉默效果明显的重组质粒,检测AQP9的sh.RNA对非酒精性脂肪性肝病(NAFLD)细胞模型的作用.方法 设计合成针对人AQP9的小干扰RNA,退火形成双链shRNA后插入pGenesil-1质粒中,并将其转染L02肝细胞,逆转录-聚合酶链反应(RT-PCR)及Western blot筛选出沉默效果明显的重组质粒.经油酸诱导L02细胞脂肪变性建立NAFLD细胞模型,通过油红O染色,测定甘油三酯、游离脂肪酸及甘油含量,检测重组质粒对NAFLD细胞模型的作用.数据比较采用方差分析.结果 经RTPCR及Western blot筛选,pshRNA-AQP9a转染组mRNA及蛋白质相对表达率为25.10％±1.19％及25.41％±1.96％,与未处理L02细胞组的39.33％±1.69％及35.08％±1.89％相比,均明显降低(P值均＜ 0.01);将重组质粒pshRNA-AQP9a转染NAFLD细胞模型能够降低其AQP9的mRNA及蛋白质表达量;油红O染色结果显示,油酸/pshRNA-AQP9a转染组细胞内脂质含量明显减少.油酸/pshRNA-AQP9a转染组细胞内甘油三酯、游离脂肪酸及甘油含量分别为(2.738±0.231) mmol/L、(1.182±0.168)mmol/L和(0.730±0.084) mmol/L,油酸组分别为(3.218±0.220) mmol/L、(1.538±0.193)mmol/L及(1.024±0.148) mmol/L,油酸/pshRNA-AQP9a转染组均明显降低(P值均＜0.05).结论 降低AQP9表达量能够减轻NAFLD细胞模型的脂肪变性程度,为进一步研究AQP9对NAFLD的基因治疗奠定基础.     

老年男性骨质疏松患者血清瘦素、胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3表达的临床意义

目的观察骨质疏松(OP)老年男性患者血清中瘦素、胰岛素样生长因子(IGF)-1和IGF结合蛋白(IGFBP)-3的表达特征,关注其临床意义。方法 68例OP老年男性患者作为观察组,38例正常骨密度、无明显器质性疾病的老年男性作为对照组。抽取两组的空腹静脉血,检测血清中瘦素、IGF-1和IGFBP-3的表达。结果观察组中瘦素、IGF-1和IGFBP-3的表达明显低于对照组,观察组中伴有骨折患者血清中瘦素、IGF-1和IGFBP-3的表达明显低于不伴有骨折患者,相关分析显示瘦素和IGF-1、IGF-1和IGFBP-3的表达均呈正相关性。结论 OP老年男性患者血清中瘦素、IGF-1和IGFBP-3低表达,瘦素和IGF-1、IGF-1和IGFBP-3均具有协同作用,三种细胞因子均参与病变形成及进展。     

肺腺癌患者血清IGF-1及IGFBP-3的测定及其与化疗疗效的关系

目的探讨肺腺癌患者血清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-3(IGFBP-3)的表达水平并比较分析其与化疗疗效的关系。方法采用ELISA法检测28例肺腺癌患者(A组),26例肺部良性疾病患者(B组)和20例健康人(C组)血清中IGF-1和IGFBP-3的含量。结果 A、B、C组血清IGF-1水平分别为(667.19±105.36)μg/L、(448.53±121.04)μg/L和(398.45±111.46)μg/L,A组明显高于B、C组,差异有统计学意义(P<0.05);B组与C组比较差异无统计学意义(P>0.05)。A、B、C组血清IGFBP-3水平分别为(3 003.17±998.23)μg/L、(3 875.43±1 017.43)μg/L和(3 964.53±1 089.73)μg/L,A组明显低于B、C组,差异有统计学意义(P<0.05);B组与C组比较差异无统计学意义(P>0.05)。12例化疗有效的患者,化疗2周期后IGF-1水平较化疗前降低,而IGFBP-3水平则较化疗前升高,但差异均无统计学意义(P>0.05)。结论血清IGF-1和IGFBP-3水平在肺腺癌的辅...     

食管癌及胃癌患者化疗前后血清IGF-1、IGF-2、IGFBP-3水平检测

采用ELISA法检测70例食管癌及胃癌患者化疗前及化疗后6周血清中人胰岛素样生长因子(IGF-1、IGF-2)及胰岛素样生长因子结合蛋白-3(IGFBP-3)水平.发现化疗有效组及化疗无效组化疗前血清IGF-1、IGF-2、IGFBP-3水平与正常对照组比较均有统计学差异;与化疗前比较,化疗有效组化疗后IGF-1明显降低、IGFBP-3明显升高,而化疗无效组化疗后IGF-1明显升高、IGFBP-3明显降低.认为血清IGF-1水平降低、IGFBP-3水平升高与食管癌、胃癌化疗疗效呈正相关,可作为预测和评价化疗疗效的指标之一.     

肥胖患者血清游离胰岛素样生长因子Ⅰ及其结合蛋白水平与代谢因素的关系

目的 观察肥胖患者血清游离胰岛素样生长因子Ⅰ(IGF-Ⅰ)、胰岛素样生长因子结合蛋白1(IGFBP-1)及IGFBP-3水平,分析其与年龄、性别、体重指数(BMI)、糖代谢、脂代谢等指标的关系。方法应用ELSA法测定97例肥胖患者和84例正常人血清游离IGF-Ⅰ、IGFBP-3、IGFBP-1、真胰岛素和血脂水平。结果 肥胖组与对照组比较,IGFBP-3明显增高(P<0.01),IGFBP-1下降(P<0.05),而游离的IGF-Ⅰ水平差异无显著性。游离IGF-Ⅰ水平与年龄呈显著负相关(正常组r=-0.26,P<0.05;肥胖组r=-0.42,P<0.01)。在肥胖组,游离IGF-Ⅰ水平与空腹血糖(r=-0.31,P<0.01)、低密度脂蛋白(r=-0.23,P<0.05)及IGFBP-1(r=-0.24,P<0.05)呈负相关,IGFBP-1与BMI(r=-0.41,P<0.01)、空腹胰岛素(FINS)(r=-0.35,P<0.01)和Homa-IR指数呈负相关(r=-0.31,P<0.01),IGFBP-3与FINS呈正相关(r=0.26,P<0.05)。结论 游离IGF-Ⅰ水平随年龄的增长有下降的趋势,并可能参与糖代谢及脂代谢的调节。IGFBP-1浓度可能反映胰岛素抵抗状态。     

非酒精性脂肪性肝病大鼠肝组织Vaspin表达及其意义探讨*

目的 研究非酒精性脂肪性肝病(NAFLD)大鼠肝组织和体外培养的脂肪变性肝细胞Vaspin表达情况及其意义。方法 采用随机数字表法随机将12只SD健康雄性大鼠分为模型组6只和对照组6只,分别采用Lieber-DeCarli 液体高脂饮食和标准饮食饲养7 w,建立模型或对照。采用免疫组织化学染色法检测肝组织Vaspin表达。采用油酸诱导法体外培养建立HepG2细胞脂肪变性模型,采用Western blot法检测细胞Vaspin蛋白表达。结果 病理学检查提示脂肪变动物模型制备成功,表现为模型组肝细胞肿胀,细胞质内可见较多脂滴;模型组肝组织Vaspin表达增强,主要分布于脂滴周围;Western blot检测结果显示脂肪变性肝细胞和对照组细胞Vaspin/GAPDH表达分别为(0.49±0.70)和(0.68±0.40),差异显著 (P <0.05)。结论 在NAFLD动物肝组织和体外培养的脂肪变性肝细胞Vaspin表达增强,可能通过影响脂滴形成而参与了NAFLD的发病。     

宫内发育迟缓与胰岛素样生长因子及其结合蛋白关系的研究

为探讨宫内发育迟缓（IUGR）的发生机制,检测了86例新生儿脐血胰岛素样生长因子－1（IGF－1）、胰岛素样生长因子结合蛋白－3（IGFBP－3）水平,并分析上述指标变化与胎儿期生长的关系。将86例新生儿分为两组,IUGR（即小于胎龄儿）组22例,适于胎龄儿（AGA）组64例,采用竞争性放射免疫分析法（RIA）测定两组脐血IGF－1水平,非竞争性免疫放射分析法（IRMA）测定IGFBP－3水平。结果显示,与AGA组相比,IUGR组脐血IGF－1和IGFBP－3水平显著降低（P＜0．001）;IGF－1水平随胎龄及出生体重增加而增加（P＜0．01）;IGFBP－3水平与胎龄及出生体重呈相关（P＜0．01）;IGF－1与IGFBP－3呈正相关（P＜0．01）。认为IUGR与IGF－1及其结合蛋白密切相关,不论何种原因引起的IUGR,其脐血IGF－1、IGFBP－3水平均低,IGF－1水平下降与IGFBP－3下降相伴随;脐血IGF－1、IGFBP－3水平与胎龄及出生体重呈正相关,随着胎龄的增加和出生体重的增长,IGF－1、IGFBP－3水平不断升高。     

Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease

Background and aims Pituitary dysfunction including growth hormone (GH) deficiency may be associated with non-alcoholic fatty liver disease (NAFLD). Since the relationships among GH, IGF-1, IGFBP-3, and development of NAFLD without hypopituitarism are unclear, we examined the role of these hormones in the development of NAFLD based on clinical, laboratory and liver histology data. Patients and methods A total of 55 consecutive patients (20 males and 35 females) with NAFLD. Results Aspartate amino transferase (AST), AST/ALT, platelet count and IGF-1, levels were significantly associated with differences in fibrosis, since these variables differed between stage 0–1 and stage 2–3 NAFLD. In multivariate analysis, platelet count (P = 0.0223, relative risk (RR), 5.899; 95% confidence interval (CI), 1.288–27.017), and IGF-1 (P = 0.0363, RR, 4.568; 95% CI, 1.101–18.945) showed significant associations with stage 2–3 NAFLD. Additionally, hyaluronic acid levels had a negative relationship with IGF-1 and the IGF-1/IGFBP-3 ratio. There was no relationship of fibrosis with GH level, but decreased GH (P = 0.0414, RR, 0.199; 95% CI, 0.042–0.989) was significantly associated with steatosis of stage 2–3. Low GH/IGF-1 and GH/IGFBP-3 ratios were found in advanced steatosis. Conclusion GH, IGF-1 and IGFBP-3 are associated with hepatic fibrosis and steatosis in NAFLD. Low levels of IGF-1 might be associated with fibrosis while low level of GH with hepatic steatosis.     

Epigenetic regulation of insulin-like growth factor axis in hepatocellular carcinoma

The insulin-like growth factor (IGF) signaling pathway is an important pathway in the process of hepatocarcinogenesis, and the IGF network is clearly dysregulated in many cancers and developmental abnormalities. In hepatocellular carcinoma (HCC), only a minority of patients are eligible for curative treatments, such as tumor resection or liver transplant. Unfortunately, there is a high recurrence of HCC after surgical tumor removal. Recent research efforts have focused on targeting IGF axis members in an attempt to find therapeutic options for many health problems. In this review, we shed lights on the regulation of members of the IGF axis, mainly by microRNAs in HCC. MicroRNAs in HCC attempt to halt the aberrant expression of the IGF network, and a single microRNA can have multiple downstream targets in one or more signaling pathways. Targeting microRNAs is a relatively new approach for identifying an efficient radical cure for HCC.     

Blood levels of insulin-like growth factors I and II in neonates of non-insulin-dependent diabetic rats

Circulating levels of insulin like growth factor I (IGF-I) and insulin like growth factor II (IGF-II) were evaluated in plasma samples during the first 72 h of life in neonates of diabetic and control mother rats. Diabetes had been induced in the diabetic dams by streptozotocin at 2 days of age. The rats developed non-insulin dependent diabetes (at 6 weeks of age) and became pregnant at 11 weeks of age. Maternal blood glucose levels were higher in the diabetic mothers (P<0.05) during the last two-thirds of gestation. Complications occurred at the end of 7.1% of the diabetic pregnancies but none of the controls. Analysis of neonates plasma glucose, IGF-I, and IGF-II concentrations in the first 12, 24, 48, and 72 h after birth revealed higher glucose levels in neonates of diabetic mothers at 72 h compared with controls (118±7 vs 85±5 mg/dl,P<0.05) but there was no difference in IGF-I or IGF-II levels between the groups at any time point. Thus, acquired impaired glucose homeostasis may be seen in neonates of mildly diabetic mothers at early stages of their life but their circulating insulin-like growth factors levels are normal. These data do not support the proposition that fetal IGF-I and —II affect the outcome of pregnancies complicated by mild diabetes in the rodent.     

胰岛素样生长因子Ⅱ及其受体在肝细胞癌变中的表达及意义

目的 探讨ＩＧＦ－Ⅱ及戎受体（ＩＧＦ－ⅡＲ）在肝细胞癌孪演化过程中的作用。方法 通过ＤＮＡ、ＲＮＡ原位分子杂交和Ｓｏｕｔｈｅｒｎ杂交技术,观察和分析慢性肝炎、肝硬化和肝癌中ＩＧＦ－Ⅱ、ＩＧＦ－ⅡＲ基因的单细胞转录瓣表达与ＨＢＶ ＤＮＡ整合之间的关系。结果 ＩＧＦ－Ⅱ、ＩＧＦ－ⅡＲ ｍＲＮＡ在慢性肝炎、肝硬化和肝癌中均有不同程度的表达,阳性率依次为：慢性肝炎（３３．３％）〈肝癌（６６．７％）〈肝硬化     

胰岛素样生长因子系统在肿瘤转移中的研究进展

胰岛素样生长因子(IGFs)系统由具有特定功能的配体(IGF-I和IGF-II)、受体(IGFR)和结合蛋白(IGFBPs)组成,在促有丝分裂,细胞转化和抑制凋亡中起重要作用,这些作用主要由IGF-I受体介导。IGFBPs是IGFs活性的调节因子。近年来研究表明IGFs系统与肿瘤的浸润和转移关系密切。     

胰岛素样生长因子对克罗恩病患者的临床意义

目的:研究我国克罗恩病(CD)患者胰岛素样生长因子水平(IGF)的变化及临床意义.方法:收集54例CD患者的临床资料,并根据临床严重程度分为轻(20例)、中(18例)、重(16例)3组.采用酶标化学发光免疫分析的方法分别检测轻、中、重各组CD患者规范性治疗前后的外周血IGF-I和胰岛素样生长因子结合蛋白-3(IGFBP3)的结果,50例健康人群作为对照组,分析外周血IGF-I和IGFBP3对CD的临床意义.结果:(1)中重度CD患者外周血IGF-I值分别为104.78μg/L±16.28μg/L和77.50μg/L±12.46μg/L,IGFBP3值分别为2.83mg/L±1.02mg/L和1.93mg/L±0.65mg/L,均较正常对照组明显减低,并随着病情加重呈进行性下降(均P<0.05).轻度组IGF-I及IGFBP3值较对照组也有所下降,但无统计学差异;(2)中重度CD经治疗有效后IGF-I值分别为122.75μg/L±27.14μg/L和102.31μg/L±29.24μg/L,IGFBP3值分别为3.85mg/L±0.92mg/L和3.35mg/L±1.35mg/L,均较治疗前明显升高(P<0.0...     

The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge

Background The insulin-like growth factor system, which includes insulin-like growth factors (IGF-I and IGF-II), IGF receptors (IGF-IR and IGF-IIR) and IGF binding proteins (IGFBPs), plays an important role in epithelial growth, anti-apoptosis and mitogenesis. There is a growing body of evidence showing that IGFs control growth and proliferation of several types of cancer. This review introduces the latest information on the biology of the IGF system and its pathophysiological role in the development of colorectal cancer.Discussion The growth promoting effects of IGF-I and IGF-II on cancer cells are mediated through the IGF-IR, which is a tyrosine kinase and cancer cells with a strong tendency to metastasise have a higher expression of the IGF-IR. Most of the IGFs in circulation are bound to the IGFBPs, which regulate the bioavailability of the IGFs. All IGFBPs inhibit IGF action by high affinity binding, while some of them also potentiate the effects of IGFs. Colon cancer cells produce specific proteases that degrade the IGFBP so that the IGF will be free to act on the cancer cell in an autocrine manner. Therefore, the IGFBPs play a crucial role in the development of the cancer.Conclusion The current knowledge about the link between IGFs and colon cancer is mainly based on in vitro investigations. Further in vivo study is needed to understand the exact role of the IGF system, especially its binding proteins, so that they can be manipulated for the prevention and treatment of colorectal cancer.