胰岛素样生长因子与肺癌

胰岛素样生长因子 (IGFs)是一组小分子多肽类物质。可以通过内分泌、自分泌和旁分泌的途径发挥促有丝分裂 ,细胞转化和抑制凋亡的作用。这些作用主要由IGF 1受体介导 ,由胰岛素样生长因子结合蛋白调节。多年的基础和临床研究已经表明 :胰岛素样生长因子与多种肿瘤的发生发展关系密切。针对IGFs轴已开展了许多治疗性的研究。本文综述了近年来IGFs的研究现状以及与肺癌关系的研究进展     

胰岛素样生长因子调节系统与骨

综述了前列腺素、白细胞介素、转化生长因子和肿瘤坏死因子等细胞因子对胰岛素样生长因子 (IGFs)调节系统的影响 ,及其基因分子生物学的调节机制。同时系统激素如生长激素、雌激素、降钙素和甲状旁腺激素等也能影响IGF调节系统。IGF调节系统与成骨细胞和破骨细胞的功能及其成骨和破骨偶联有着密切关系 ,其中IGF可能发挥着核心作用。     

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.     

急性脑梗死患者血清胰岛素样生长因子1和胰岛素样生长因子结合蛋白3水平的变化

为探讨急性脑梗死患者血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平的动态变化及其临床意义 ,采用酶联免疫吸附试验双抗体夹心法检测 6 0例急性脑梗死患者 (发病后第 3天及第 14天 )和 30例正常人血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平 ,并根据影像学结果所显示的梗死灶的直径将所有患者分为大梗死组、中梗死组和小梗死组 ,分析梗死灶大小对血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平的影响。结果发现脑梗死组发病后第 3天和第 14天血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平均显著低于正常对照组 (P <0 .0 0 1) ,脑梗死组发病后第 3天血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平显著低于第 14天 (P <0 .0 0 5 ) ;不同大小梗死灶组之间 (发病后第 3天和 14天 )血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平差异显著 (P <0 .0 0 1)。以上提示胰岛素样生长因子 1可能对脑缺血区的神经元具有保护作用 ,而且血清胰岛素样生长因子 1和胰岛素样生长因子结合蛋白 3水平受梗死灶大小的影响     

COPD患者血清胎盘生长因子水平的研究

目的探讨慢性阻塞性肺疾病（COPD）患者血清胎盘生长因子在发病机制中的作用。方法采用酶联免疫吸附试验法检测COPD组42例和对照组42例血清胎盘生长因子水平,并与COPD患者FEV1占预计值％和COPD严重程度进行相关分析。结果COPD组血清胎盘生长因子水平高于对照组（28．30±14．30pg／ml vs 6．8±3．12pg／ml,P〈0．01）。COPD组FEV1占预计值％与血清胎盘生长因子水平呈负相关（r=-0．52,P〈0．01）。COPD病情严重程度与血清胎盘生长因子水平正相关（r=0．61,P〈0．01）。结论COPD组血清胎盘生长因子水平高于对照组,且与COPD的严重程度呈正相关。胎盘生长因子在COPD发病机制中起一定作用。     

胰岛素样生长因子在肾透明细胞癌患者血液中表达及其临床意义

目的 探讨胰岛素样生长因子(IGF)Ⅰ、Ⅱ和胰岛素样生长因子结合蛋白(IGFBP)3、5在肾透明细胞癌患者外周血液中的表达及其临床意义.方法 选择2007年5月至2009年12月在我院手术治疗的肾透明细胞癌患者40例(肾癌组),对照组为同期的肾积水患者16例,采用酶联免疫吸附法(ELISA)检测两组患者血清标本中IGF-Ⅰ、Ⅱ和IGFBP3、5的水平.结果 肾癌组术前血清IGF-Ⅰ、Ⅱ和IGFBP3、5分别为985.7μg/L、1154.0μg/L和46.6 μg/L、9.6 μg/L,术后分别为431.4μg/L、632.6μg/L和26.7 μg/L、6.7μg/L差异均有统计学意义(P值分别为0.001、0.009、0.001、0.002);肾积水组IGF-Ⅰ、Ⅱ和IGFBP3、5水平术前术后比较,差异无统计学意义(P＞0.05).结论 IGF-Ⅰ、Ⅱ和IGFBP3、5在肾透明细胞癌患者的血液中呈现高表达,IGF-Ⅱ具有临床诊断意义.

Abstract：

Objective To observe the expressions of serum insulin-like growth factor (IGF)- Ⅰ ,Ⅱ and IGF binding protein (IGFBP) 3, 5 and to explore the clinical significances in patients with clear cell carcinoma of kidney. Methods Enzyme-linked immunosorbent assay (ELISA) methods were adopted to examine serum expressions of IGF-Ⅰ , Ⅱ and IGFBP 3, 5 in 40 cases with clear cell carcinoma of kidney (renal carcinoma group) and 16 cases with hydronephrosis (control group) from May 2007 to December 2009. Results IGF- Ⅰ , Ⅱ and IGFBP 3,5 in renal carcinoma showed higher expressions before operation (985. 7 μg/L, 1154.0 μg/L,46.6 μg/L and 9.6 μg/L, respectively)than after operation (431.4 μg/L, 632.6 μg/L, 26.7 μg/L, and 6.7 μg/L, respectively, all P＜0. 05 ～0.01). There were no significant differences in those indexes between pre- and post- operation in control group (P＞ 0. 05). Conclusions There are high expressions of serum IGF-Ⅰ , Ⅱ and IGFBP 3, 5 in renal carcinoma patients, and IGF- Ⅱ has clinical significance in diagnosis.     

胃癌组织中胰岛素样生长因子受体的表达及意义

目的探讨胰岛素样生长因子Ⅰ、Ⅱ受体（IGF-ⅠR、IGF-ⅡR）表达与胃癌分型、分期、浸润和转移等生物学行为的关系。方法选择67例胃癌患者（胃癌组）手术标本,16例慢性萎缩性胃炎患者（CAG组）和13例慢性萎缩性胃炎伴重度异型增生患者（CAGD组）胃镜活检标本,采用免疫组化SP法检测各组IGF-ⅠR、IGF-ⅡR的表达,并与胃癌的生物学行为进行相关性分析。结果胃癌组IGF-ⅠR阳性表达率为64.2%,胃癌组和CAGD组IGF-ⅠR阳性表达率均明显高于CAG组（P〈0.01或〈0.05）;胃癌组IGF-ⅡR阳性表达率为59.7%,较CAG组明显升高（P〈0.01）。IGF-ⅠR阳性表达与胃癌的分化程度、浸润深度、肿瘤大小、淋巴结转移及TNM分期均密切相关（P均〈0.05）,IGF-ⅡR仅与胃癌的分化程度密切相关（P〈0.05）。结论 IGF-ⅠR、IGF-ⅡR的过表达均与胃癌的生物学行为有关,但IGF-ⅠR的关系更密切,两者联合检测可作为胃癌手术治疗及评估预后的参考指标。     

自发性高血压大鼠血浆和组织胰岛素样生长因子-1含量的变化

为了探索胰岛素样本生长因子－１在自发性高血压大鼠体内的改变与自发性高血压发生发展的病理生理过程中的关系，用放射免疫分析法测定正常和自发性高血压大鼠血浆和组织中胰岛素样生长因子－１含量。     

人重组胰岛素样生长因子1对慢性阻塞性肺疾病大鼠膈肌细胞凋亡的保护作用及机制探讨

目的 探讨人重组胰岛素样生长因子1(rhIGF-1)对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠膈肌细胞凋亡的保护作用及其可能机制.方法 雄性Wistar大鼠45只,随机分为对照组(A组),COPD模型组(B组),COPD模型+rhIGF-1干预组(C组),每组15只.第1天、第14天和第28天各组处死5只,取完整膈肌称重后用原位末端标记法测定各组膈肌细胞凋亡率,免疫组织化学法测定膈肌细胞Fas蛋白表达情况,RT-PCR检测各组膈肌细胞Fas基因表达水平.结果 第28天后B、C组膈肌质量均小于A组,C组大于B组(P＜0.05).同一时间点B、C组膈肌细胞凋亡率.Fas蛋白阳性细咆率及Fas基因表达水平均大于A组,C组小于B组(P＜0.05).结论 Fas/FasL介导的凋亡途径参与了膈肌凋亡的发生,rhIGF-1可能通过干预Fas/FasL途径减少了膈肌凋亡,对COPD大鼠的膈肌凋亡产生保护作用.     

Role of angiogenesis and vascular remodeling in chronic obstructive pulmonary disease

Recently, angiogenesis and pulmonary vascular remodeling in COPD has been investigated. It has been hypothesized that endothelial dysfunction might be an initiating event that promotes vessel remodeling in COPD.Inflammatory tissue- a pivotal pathological feature of COPD- often hypoxic, can induce angiogenesis through upregulation of factors such as VEGF or FGF and regulators of angiogenesis such as chemokines (CXC family), acting either as angiogenic or angiostatic. Angiopoietins are distinct molecules that act in association with VEGF at different stages of angiogenic process. The regulation of angiogenesis is determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively, not yet elucidated in detail in COPD.Recent studies suggested an increased expression of VEGF in pulmonary muscular arteries of patients with moderate COPD and also in smokers with normal lung function. This was also associated with enlargement of the arterial wall. However, in patients with severe emphysema, the expression of VEGF tended to be low, despite intense vascular remodelling. Furthermore, it has been suggested that VEGF might be involved in the pathogenesis of emphysema through apoptotic mechanisms. Experimental studies showed that the lung microvascular endothelial cells (including the alveolar septal capillary cells) are particularly vulnerable and dependent on VEGF for their survival. Apoptosis of endothelial, leading to the loss of capillaries may well be a central mechanism in patients with emphysema and muscle wasting.This review article summarizes the current knowledge regarding the contribution of vascular remodeling, as well as the pathogenetic and therapeutic implications of pivotal angiogenic mediators, in COPD.     

Falls in patients with chronic obstructive pulmonary disease: A call for further research

Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress. The effects of COPD, however, are not exclusively limited to respiratory function and people with COPD face many non-respiratory manifestations that affect both function and mobility. Deficits in function and mobility have been associated with an increased risk for falling in older adults. The purpose of this study was to provide a theoretical framework to identify risks factors for falls in people with COPD. We have analyzed the literature to identify possible relationships between pathophysiological changes observed in COPD and common risk factors for falls. Well-established fall risk factors in people with COPD include lower limb muscle weakness and impaired activities of daily living. Other intrinsic risk factors such as gait and balance deficits, nutritional depletion, malnutrition, depression, cognitive impairments and medications are possible risk factors that need to be confirmed with more studies. There is no evidence that visual deficits are common in COPD. The role that precipitating factors such as syncope and postural hypotension may have on fall risk is unclear. Exacerbations and dyspnea do not have a precipitating effect on fall risk but they contribute to the progressive physical deterioration that may theoretically increase the risk for falls. While these results suggest that people with COPD might have an increased susceptibility to fall compared to their healthy peers, further research is needed to determine the prevalence of falls and specific risk factors for falls in people living with COPD.     

NOS在慢性阻塞性肺病急性发作期的研究

目的:为研究一氧化氮合成酶(NOS)在慢性阻塞性肺病急性期发作的变化。方法:选择实验组及对照组各30例，并检测(NOS)的酶活性，实验组NOS的酶活性明显高于对照组，两组间有显性差异。结论:NOS的醇活性在慢性阻塞性肺病患急性发作期明显增高。     

支气管肺泡灌洗液组织蛋白酶S与慢性阻塞性肺疾病严重程度的关系

目的探讨慢性阻塞性肺疾病(COPD)患者支气管肺泡灌洗液(BALF)中组织蛋白酶S在综合评估分组中的价值。方法入选2014年4月至2017年4月在上海市第六人民医院呼吸内科门诊随诊的COPD稳定期患者46例,根据COPD综合评估(CAT)结果分为4组:A组[CAT10分、第1秒用力呼气容积(FEV1)占预计值百分比≥50%且近1年急性加重次数2次]11例,B组(CAT≥10分、FEV1占预计值百分比≥50%且近1年急性加重次数2次)7例,C组(CAT10分、FEV1占预计值百分比50%或近1年急性加重次数≥2次)13例,D组(CAT≥10分、FEV1占预计值百分比50%或近1年急性加重次数≥2次)15例。同期纳入肺功能正常的健康自愿者29例作为对照组。酶联免疫吸附测定法(ELISA)测定BALF中组织蛋白酶S。高分辨率CT测量低衰减区域(LAA)占全肺体积的百分比(LAA%)。采用SPSS 16.0统计软件进行数据分析。结果 COPD组BALF中组织蛋白酶S水平显著高于对照组;组织蛋白酶S水平在不同病情严重程度中表现为:D组C组B组A组(P0.01);在不同肺气肿程度中表现为:LAA 3级LAA 2级LAA 1级LAA 0级(P0.01)。单因素分析提示,LAA分级可显著影响组织蛋白酶S水平(F=5.141,P0.001)。相关分析结果提示,COPD患者BALF中蛋白酶S水平与前1年急性加重频率(r=0.142,P=0.003)、CAT评分(r=0.309,P=0.017)、LAA%(r=0.497,P0.001)呈显著正相关。结论组织蛋白酶S水平能够反映COPD严重程度,可作为判断COPD病情严重度的标志物,具有一定的治疗指导作用。     

Outpatient pulmonary rehabilitation in patients with chronic obstructive pulmonary disease

Objective

To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD, using St.George’s Respiratory questionnaire (SGRQ), the 6-minutes walking test (6-MWT) and BODE index as the primary outcome measures.

Methods

A prospective, parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD (67 men and 13 women; mean age 64.8 ± 10.6 years; FEV₁, 42.8% ± 7.6% of the predicted value. The active group (n = 40) took part in a 14-week rehabilitation program [3 h/wk, 1.5 h of education and exercise and 1.5 h of cycling]. The control group (n = 40) was reviewed routinely as medical outpatients. The following evaluations were carried out at study entry and after14 weeks: (1) pulmonary function studies; (2) 6-minutes walking test 6MWT; (3) quality of life; and (4) BODE index.

Results

The following patients completed the study: 35 patients (87.5%) from the active group (mean age, 63.7 ± 11.9 years; mean forced expiratory volume in one second (FEV₁), 41.9 ± 2.6% of the predicted value); and 36 patients (88%) from the control group (mean age, 65.9 ± 10.3 years; mean FEV₁, 43.33 ± 3.6% of the predicted value). We found no changes in pulmonary function parameters in the active group and the control one at 14weeks. On the other hand, there were significant changes within the components of the SGRQ (12.3 for the score total) for the patients of the active group but not for the patients of the control one (only 1.5 for the score total), we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one, and finally a decrease of two points (from 6 to 4) was noted in the score of the active group’s BODE index without any change in the control group’s one.

Conclusion

An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD, and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index.     

慢性阻塞性肺疾病患者夜间低氧发生情况的初步探讨

目的探讨慢性阻塞性肺疾病（COPD）患者夜间低氧的发生情况并探讨其发病机制。方法将60例COPD稳定期患者分为两组：非呼吸衰竭组（40例）、呼吸衰竭组（20例）,另选急性肺炎治愈患者作为对照组（20例）。采用东方万泰公司提供的便携式初筛诊断仪进行睡眠监测。结果夜间低氧血症在三组的发生率分别为45％、100％及10％,COPD组明显高于对照组（P〈0．05）。夜间低氧与日间血氧饱和度（SaO2）相关。结论COPD患者夜间睡眠时出现低氧或低氧血症加重,夜间低氧血症可通过白天SaO2来预测,COPD与睡眠暂停低通气综合征（OSAHS）并存可加重夜间低氧血症。     

长期家庭氧疗对缓解期COPD患者的影响研究

目的观察长期家庭氧疗对缓解期COPD患者的肺功能及血气影响。方法选择60例缓解期COPD患者随机分为两组,笫1组单纯家庭氧疗（每天15小时以上）,笫2组不给予氧疗,1年后观察两组FEV1%预计值、血气的变化情况。结果氧疗组FEV1%预计值、动脉血氧分压明显高于对照组（P〈0.01）。结论长期家庭氧疗可以改善COPD患者的动脉血氧分压和肺功能。     

老年COPD肺心病患者血清甲状腺激素的观察分析

目的探讨老年COPD肺心病患者血清甲状腺激素水平的变化。方法用放射免疫法分别测定COPD合并肺心病急性发作组42例,缓解组30例,对照组35例,血清TT3、FT3、TT4、FT4和TSH水平,同步抽取外周动脉血作血气分析,并对数据进行统计学分析。结果COPD合并肺心病急性发作各组血清TT3,FT3,IT4,FT4均值均明显低于对照组（P〈0．05或P〈0．01）,亦低于缓解期患者（P〈0．05）,差异有显著性。血清TSH在各组之间差异无统计学意义。经治疗,心功能改善后,血清TT3,FT3,TT4,FT4显著回升,TSH无显著性变化（P〉0．05）。结论老年COPD合并肺心病患者,存在低甲状腺激素综合症,血清甲状腺激素水平有助于判断病情的严重程度,亦有助于疗效观察及估计预后。     

Home respiratory muscle training in patients with chronic obstructive pulmonary disease

OBJECTIVE AND BACKGROUND: The benefits of inspiratory muscle strength training in decreasing symptoms, disability or handicap of patients affected by COPD are not well established. The objective of this study was to assess the efficacy of the constant use of a new flow-volumetric inspiratory exerciser, named Respivol, in improving respiratory functional parameters in COPD patients. METHODS: Twenty consecutive ambulatory patients affected by COPD were enrolled. Each patient was assessed, before and after 3 and 6 months inspiratory exercise with Respivol, for the following clinical parameters: maximal inspiratory pressure, maximal expiratory pressure, dyspnoea grade, quality of life by a self-administered St George questionnaire and a 6-min walking test. After a brief progressive ambulatory training programme, inspiratory exercise with Respivol was performed at home for 6 months. All patients used Respivol together with medical treatment. RESULTS: Maximal inspiratory pressure and maximal expiratory pressure values were significantly increased after 3 and 6 months of exercise. Dyspnoea grade was significantly reduced and the 6-min walking test showed an increase in effort tolerance, after 6 months of home training. Quality of life assessment showed an improvement, associated with a decrease of respiratory disease symptoms. CONCLUSIONS: Inspiratory muscle strength training with Respivol seems to be efficient in reducing symptoms and improving quality of life in adults with COPD.