Sarchielli Paola, Di Filippo Massimiliano, Ercolani Maria Vittoria, Chiasserini Davide, Mattioni Alessia, Bonucci Michele, Tenaglia Serena, Eusebi Paolo, Calabresi Paolo
Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Italy.
Neurosci Lett. 2008 Apr 25;435(3):223-8. doi: 10.1016/j.neulet.2008.02.040. Epub 2008 Feb 26.
In recent years a role has been recognized for fibroblast growth factor (FGF)-2 in the pathogenesis of demyelination and the failure of remyelination in experimental models of multiple sclerosis (MS). FGF-2 levels were determined using a sensitive immunoassay in the cerebrospinal fluid (CSF) of 20 patients with clinically isolated syndrome (CIS), 40 patients with relapsing-remitting (R-R) MS, and 30 patients with secondary progressive (SP) MS, correlated with MRI measures. Control CSF samples were obtained from 20 subjects who underwent lumbar puncture for diagnostic purposes and for whom all instrumental and laboratory analyses excluded systemic and nervous system diseases. FGF-2 levels in the CSF of MS and CIS patients were significantly higher than controls (P<0.001 and P<0.05, respectively). The highest levels were detected in R-R MS patients during relapse and in SP MS patients with an increase of 1 point in EDSS scores in the last 6 months. A significant correlation was found in SP MS patients with lesional load (R=0.43, P<0.01) but not with parenchymal fractions as measures of brain atrophy. A slight increase in serum FGF-2 levels was also found in R-R MS patients during relapse with gadolinium enhancing lesions and in SP patients with disability progression. These findings support the implication of FGF-2 in the pathogenesis of MS and concur with recent reports of the involvement of FGF receptor signalling in the disruption of myelin production in differentiated oligodendrocytes and in the loss of adult oligodendrocytes and myelin in vivo due to FGF-2.
近年来，在多发性硬化症（MS）实验模型中，成纤维细胞生长因子（FGF）-2在脱髓鞘发病机制及髓鞘再生失败过程中的作用已得到认可。采用灵敏免疫分析法测定了20例临床孤立综合征（CIS）患者、40例复发缓解型（R-R）MS患者和30例继发进展型（SP）MS患者脑脊液（CSF）中的FGF-2水平，并与MRI测量结果进行关联分析。对照CSF样本取自20例因诊断目的接受腰椎穿刺且所有仪器和实验室分析均排除系统性和神经系统疾病的受试者。MS和CIS患者CSF中的FGF-2水平显著高于对照组（分别为P<0.001和P<0.05）。R-R MS患者复发期及过去6个月内扩展残疾状态量表（EDSS）评分增加1分的SP MS患者中检测到的FGF-2水平最高。在SP MS患者中发现FGF-2水平与病灶负荷存在显著相关性（R=0.43，P<0.01），但与作为脑萎缩指标的实质部分无相关性。在伴有钆增强病灶的R-R MS患者复发期及残疾进展的SP患者中，血清FGF-2水平也略有升高。这些发现支持FGF-2参与MS发病机制的观点，与近期有关FGF受体信号传导参与分化少突胶质细胞髓鞘生成破坏以及体内成年少突胶质细胞和髓鞘因FGF-2而丢失的报道一致。
