纤维连接蛋白在糖尿病足溃疡中的研究进展

<正>据估计,15%的糖尿病患者在他们的一生中会发生足溃疡,且溃疡创面难以愈合~[1],是导致糖尿病患者致残、致死的严重慢性并发症之一。糖尿病足治疗是个系统工程,全方位统筹使足部动脉血液供应改善、感染的有效控制和血糖达标,这是治疗的重点~[2]。而纤维连接蛋白(FN)具有促进细胞间、细胞与基质间的粘连,维持细胞形态,促进细胞移动,引导分化,调理吞噬和促进组织修复等多种功能,能显著促进溃疡伤口愈     

冠心病猝死患者心肌组织纤维连接蛋白及内皮素的表达

目的探讨冠心病猝死患者心肌组织中纤维连接蛋白、内皮素的表达情况。方法选择150份冠状动脉组织切片标本,其中正常血管标本50份,动脉粥样硬化稳定斑块50份和不稳定斑块50份,用MaxVision免疫组化方法对比检测纤维连接蛋白(FN)和内皮素(ET)的表达。结果正常心肌组织FN、ET均呈阴性表达;稳定斑块组FN呈散在、单个细胞性胞质棕褐色着色,ET呈局灶性心肌细胞胞质阳性表达;不稳定斑块组FN呈大片状心肌细胞胞质棕褐色着色,ET呈血管平滑肌、血管内皮及心肌细胞胞质呈棕色阳性着色。3组患者心肌中ET、FN阳性反应物累积吸光度值比较均具有统计学意义(P0.05)。结论 FN和ET的阳性表达是心肌缺血和损伤的灵敏指标,对推断冠心病猝死具有一定的实际应用价值。     

纤维连接蛋白在大鼠肺纤维化中的作用

目的 研究纤维连接蛋白(FN)在肺纤维化中的作用。方法 用免疫组织化学方法观察实验性大鼠肺纤维化纤维连接蛋白（FN）的动态变化;用Northem印迹杂交和免疫细胞化学方法分别观察FN对体外培养的大鼠肺成纤维细胞I、Ⅲ型前胶原mRNA和蛋白表达的影响。结果（1）实验性肺纤维化大鼠肺组织内FN的含量持续增多;（2）体外培养的肺成纤维细胞经FN作有2h,I、Ⅲ型前胶原mRNA的表达即增强,分别在12h、6h达到最大值,平均吸光度（A值）为对照组的1．7、3．2倍;I、Ⅲ型前胶原蛋白的表达亦增强（P＜0．01）。抗FN受体的抗体能部分抑制FN对胶原表达的上调作用（P＜0．05）。结论 FN能够促进大鼠肺成纤维细胞合成I、Ⅲ型胶原、其调控机制之一是在转录水平上增强了前胶原mRNA的表达。     

纤维连接蛋白肾小球病

纤维连接蛋白肾小球病 ,也称纤维连接蛋白沉积肾小球病 (glomerulopathywithfibronectindeposits ,GFND) ,是近年来才被认识的一种遗传性肾小球病 ,其发病较为罕见。据不完全统计 ,自 1980年以来 ,全世界共报道了约 13个家系 ,患者总数约 4 8人[1～ 10 ] 。GFND病例始先报道于欧美国家 ,1998年日本人Sato等[8] 报道了亚洲第一例GFND ,随后日本人Uesugi等[9] 又报道了 4个家庭的 5例患者 ,而我国尚未见报道。本文就GFND的命名、临床表现、病理改变、诊断和鉴别诊断、治疗、遗传学特征、相关基因研究以及发病机制作一综述。1　命　　…     

纤维连接蛋白与肝脏疾病的关系

纤维连接蛋白(Fibronectin,FN)是一族分子结构、理化性质、免疫学性质均相似的高分子糖蛋白,体内分布甚广。该蛋白由 Morrison 氏等首次发现,称为冷不溶性球蛋白(CIG)。1976年 Kuusela 氏等将它命名为纤维连接蛋白。目前认为 FN 与多种疾病状态有关,如肝、肾疾病、创伤、感染、休克等,其中以 FN 与肝脏病的关系较为密切。下面就近年来国内外文献关于肝脏病时 FN 的研究结果作一简述。     

纤维连接蛋白及其受体在免疫性心肌炎小鼠心肌的表达

目的观察纤维连接蛋白（FN）及其受体CD29在实验性自身免疫性心肌炎（EAM）中的表达情况。方法人工合成心肌肌球蛋白致病性抗原表位多肽,与弗氏完全佐剂（CFA）混合,在1d和8d免疫实验组小鼠（多肽剂量:100μg/只）,诱发EAM;对照组则给予PBS与CFA混合液。分别于21d及75d,检测心肌炎症评分、胶原容积分数（CVF）、Ⅲ型胶原（COLⅢ）mRNA的表达、FN及CD29的表达。结果21d时,实验组小鼠心肌炎性浸润明显,间质出现少量胶原沉积,COLⅢmRNA、FN及CD29的表达均显著高于对照组（均P<0.01）。至75d时,实验组小鼠心肌炎性浸润显著减少,间质胶原沉积更加明显,COLⅢmRNA的表达进一步上调（P<0.05）,FN的表达有所下降,CD29的表达则显著降低（P<0.01）,但仍显著高于对照组（P<0.01）。结论在EAM时,FN及其受体在心肌的表达上调,可能参与了自身免疫性炎症损伤、组织修复及纤维化改变过程,从而促进心肌炎向心肌病的转化。     

纤维连接蛋白在肝纤维化形成和发展中的作用

细胞外基质（ECM）在多种组织中不仅起机械性支架的作用,而且还具有调节细胞增殖、分化、迁移以及基因表达等作用,在细胞间通讯网络中具有中心性位置。现在已经越来越清楚,在肝脏损伤后纤维化发生的过程中,ECM不仅仅是在间质中被动地沉积,它还是纤维化的主动参与者。本文主要综述了纤维连接蛋白（fibronectin,FN）在肝纤维化发生发展中的作用。1FN结构及其功能FN是一种分子量440KD的糖蛋白,存在几种亚型,都是由于其初级转录产物的三个“血型”剪接部位剪接方式的不同所产生。三个“III型”区域中有两个（EIIIA和EIIIB）…     

胎儿纤维连接蛋白检测在早产预测中的临床应用

目的:对胎儿纤维连接蛋白(f FN)检测在早产预测中的临床应用展开分析。方法:资料选择常规产检诊断为先兆早产的孕妇65例作为观察组,选择同期65例正常孕妇作为对照组,两组均进行阴道分泌物f FN检测,并对检测结果作回顾性分析与对照。结果:观察组65例先兆早产的孕妇中,经f FN检测为阳性者37例,阳性率为56.92%;对照组正常孕妇的f FN检测阳性者3例,阳性率为4.62%,两组f FN检测结果差异有统计学意义(P<0.05);且观察组中f FN测定为阳性者于7 d、14 d、孕37周内分娩率明显高于f FN阴性者,差异有统计学意义(P<0.05)。结论:胎儿纤维连接蛋白检测在早产预测中具有较高的临床价值,值得临床推广应用。     

纤维连接蛋白肾小球病

病例摘要 病史患者男性，45岁，因视物不清、水肿发现高血压及尿检异常6年于2007-08-28入院。     

Intraglomerular fibronectin accumulation and degradation in obese Zucker rats

Summary The obese Zucker rat is a classic model of non-immune mediated spontaneous focal glomerulosclerosis. An important initiating hallmark of glomerulosclerosis in this model is mesangial matrix expansion. Fibronectin, a highly biologically active glycoprotein, is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay we assessed the intraglomerular fibronectin content and its degradation in obese Zucker rats and their lean littermates. In the obese Zucker rats the glomerular fibronectin content was significantly higher in comparison to the controls (88±6 vs 48±4 ng/10³ glomeruli). Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats when compared to control animals (at pH 5.4: 186±6 U/mg protein vs 286±14 U/mg protein, at pH 7.4: 152±12 U/mg protein vs 193±12 U/mg protein). These data demonstrate that in obese Zucker rats there is a glomerular accumulation of fibronectin which we propose is at least partly due to diminished proteolytic digestion. Whether accumulation of intraglomerular fibronectin contributes to progressive glomerulosclerosis remains a matter of debate.     

GIRK4在肥胖大鼠脂肪组织中的表达

目的 研究饮食诱导肥胖大鼠G蛋白耦联(门控)内向整流钾离子通道(GIRK4)基因在脂肪组织中的表达,探讨其与肥胖的相关性.方法 30只Sprague-Dawley大鼠随机分为两组:对照组(n=10),予以普通饲料饲喂;肥胖组(n=20),予以高脂肪、高热量饮食饲喂.8周后处死大鼠,提取两组的白色脂肪组织和棕色脂肪组织,...     

内质网应激相关基因在肥胖患者内脏脂肪组织中表达水平观察

肥胖患者网膜脂肪组织中内质网应激相关基因重链结合蛋白(Bip)、肌醇需求激酶1(IRE1)、类PKR的内质网激酶(PERK)及氧调节蛋白150(ORP150)的mRNA表达量明显高于正常体重者[1.4(1.4)对0.9(0.6)、2.0±0.8对1.3±0.8、2.4(2.9)对1.5(1.2)、1.6(2.6)对0.6(0.5),均P<0.05],PERK和ORP150的表达量与体重指数相关,Bip、ORP150、X盒结合蛋白1(XBP1)及IRE1表达量与肿瘤坏死因子α、白细胞介素6表达量相关,提示肥胖患者内脏脂肪组织中内质网应激被激活,内质网应激相关基因表达和局部炎症相关.     

肥胖患者大网膜脂肪脂联素mRNA表达及相关因素的研究

选择43例择期外科手术患者，用RT-PCR法检测大网膜脂肪组织脂联素表达水平。发现肥胖患者的大网膜脂肪组织中脂联素表达明显降低，腹型肥胖、胰岛素抵抗以及肿瘤坏死因子-α是大网膜脂肪组织脂联素表达水平的主要影响因素。     

肥胖患者脂肪组织抵抗素基因mRNA表达的研究

19例肥胖者与20例体重正常者的网膜脂肪与皮下脂肪的研究显示，抵抗素基因表达量，肥胖者与体重正常者无差异，网膜脂肪与皮下脂肪无差异。这提示，抵抗素基因表达与胰岛素抵抗无关。     

Changes in lung tissue fibronectin content and synthesis during postnatal lung growth

We studied changes in lung tissue fibronectin content and synthesis during postnatal lung growth in rats. We reasoned that fibronectin, which is important in cell differentiation, migration, and adhesion, and in the organization of the extracellular matrix, might play a role in the rapid cell proliferation and alveolar septal formation that occurs postnatally in mammalian lungs. Newborn rats were sacrificed at 4, 7, 11, 14, and 21 days after birth. The lungs were perfused and lavaged, tissue fibronectin was extracted using urea and heparin (Bray et al, Science 1981; 214:793) and the extracted fibronectin was measured by enzyme-linked immunoassay. Tissue fibronectin synthesis was measured by the in vivo incorporation of 35S-methionine into fibronectin that was extracted from lung tissue and immunoprecipitated. Lavage fibronectin and albumin content and lung tissue collagen (hydroxyproline) content were also determined. Lung tissue fibronectin content per g dry lung almost doubled between days 4 and 7 after birth, was slightly higher at day 14 than at day 7, and decreased sharply between days 14 and 21. Lung tissue fibronectin synthesis per g dry lung increased steadily between days 4 and 14 to reach a peak value of about 2.5 times the 4-day value; it then decreased sharply between days 14 and 21. The period of increased fibronectin content and synthesis (4 to 14 days) coincided with the period during which lung cell proliferation and secondary alveolar septa formation are known to be the most active, and the sharp decrease in fibronectin content and synthesis (between 14 and 21 days) coincided with the period during which lung growth and remodeling markedly decrease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Obesity and kidney disease

The prevalence of obesity worldwide has increased dramatically. Besides, an approximately two-fold higher rate of increase in mean BMI among the incident ESRD has been reported in the US population from 1995–2002. Chronic kidney disease (CKD) prevalence increases from 2.9% among adults with an ideal BMI to 4.5% among obese adults. The development of CKD is usually the culminating result of the interaction of multiple risk factors. Obesity represents one example of a multitoxicity state and given the background of genetic susceptibility and/or reduced nephron number, overweight may initiate renal remodeling and/or accelerate kidney failure. Obesity may be the number one preventable risk factor for CKD. Weight loss has indeed been shown to improve glomerular hemodynamics and reduce urine albumin excretion. Thus, obese patients with CKD should be counseled on the benefits of weight loss.     

Diagnostic relevance of fibronectin in cryoprecipitates

Summary Fibronectin is a known component of plasma cryoprecipitates. It is seen in cryoglobulins from patients with monoclonal gammopathies and also from rheumatoid arthritis, and patients with systemic lupus erythematosus and other connective tissue diseases. We evaluated the clinical relevance of measures of cryoprecipitable fibronectin from the sera of 88 patients with rheumatic diseases and 27 healthy controls. There were 28 patients with rheumatoid arthritis, 19 with systemic vasculitis, 5 with cutaneous vasculitis, and 36 with a systemic connective tissue disorder. We measured total and cryoprecipitable fibronectin and for comparison immunoglobulins G, A, and M and complement C3 and C4. Cryoprecipitable fibronectin was detected in 33% control sera and 42% patient sera. The mean levels were higher in the sera of patients in all diagnostic groups. The highest levels were seen in rheumatoid patients with systemic disease, systemic vasculitis, and connective tissue diseases. The presence of cryoprecipitable fibronectin was related to the clinical activity of systemic vasculitis; none of the 6 patients with clinically inactive vasculitis had detectable fibronectin in their cryoprecipitates; but it was seen in 7 to 13 cases with active vasculitis. There were only weak relationships between cryoprecipitable fibronectin and immunoglobulin and complement levels in cryoprecipitates. We conclude that routinely measuring fibronectin levels in cryoprecipitates is generally of doubtful diagnostic value. However, it appears to be a useful marker of the clinical activity of systemic vasculitis and we recommend its use in the laboratory assessment of vasculitis.     

Differences between plasma and synovial fluid fibronectin

Summary Fibronectin is a high molecular weight glycoprotein of plasma and tissue fluids, and one of its functions is to opsonise particulate material. Chromatographic and electrophoretic analyses showed that the main components of fibronectin are biochemically similar in rheumatoid patients' plasma and synovial fluid. But synovial fluid fibronectin also contains a slow-moving component seen on two-dimensional immunoelectrophoresis, suggesting the presence of fibronectin complexes. Affinity chromatography provided evidence that these involved IgG, and in vitro studies showed that fibronectin influenced the reaction between IgG and anti-IgG. Synovial fluid fibronectin is functionally active in binding to gelatin in an haemagglutination assay, and it gave a relatively higher degree of haemagglutination than did plasma fibronectin, supporting the concept of multivalent fibronectin complexes in synovial fluid. These results suggest synovial fluid fibronectin may be involved in the opsonic removal of IgG-containing complexes from synovial fluid.