Sabuncuoğlu Hakan, Bavbek Murad, Sabuncuoğlu Bizden, Gadelha Eberval, Köse Kenan, Preul Mark
Department of Neurosurgery, Ufuk University School of Medicine, Ankara, Turkey.
Spine J. 2007 Jul-Aug;7(4):459-65. doi: 10.1016/j.spinee.2006.06.398. Epub 2007 Apr 6.
Data from studies in other diseases state implicate cellular adhesion molecules as mediators of fibrosis and scarring. We sought to explore and assess the effect of using monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) and its ligand CD-18 to decrease epidural fibrosis in an animal spinal surgery model.
We hypothesize that use of antiadhesion molecules (anti-ICAM-1 and anti-CD-18) decreases epidural fibrosis in rats after spinal surgery compared with nontreated group and monoclonal anti human immunoglobulin (Ig)G group.
Experimental animal spine surgery (laminectomy) protocol with application of antiadhesion molecules (anti-ICAM-1 and anti-CD-18 group as a specific monoclonal antibody) to surgical site in test group compared with monoclonal antihuman IgG group (as a nonspecific monoclonal antibody) and nontreated group.
Thirty Sprague Dawley male or female rats weighing 175 to 250 g were used randomly for three groups (nontreated, anti-ICAM-1 and anti-CD-18, monoclonal antihuman IgG). Laminectomy was performed at level L4 in all animal groups. After injection of materials (except nontreated group), the surgical sites were closed in layers. Three weeks later, all rats were killed. Twenty-seven rats were available for histological analysis. The histological sections were evaluated for fibroblast numbers of fibrous tissue within the laminectomy side, adhesion degree between dura mater and fibrous tissue, and new bone formation in the laminectomy region.
Comparing the fibroblast numbers in fibrous tissue within groups, the number of fibroblasts were significantly less in anti-ICAM-1 and anti-CD-18 group than nontreated group (p=.037). The number of fibroblasts of monoclonal anti human IgG group was not significantly different from anti-ICAM-1 and anti-CD-18 (p=.608) and the nontreated group (p=.508). In the anti-ICAM-1 and anti-CD-18 applied group, adhesion degree was found significantly less than monoclonal antihuman IgG (p=.036) and nontreated group (p=.036) statistically. There were no significant difference between the monoclonal antihuman IgG group and the nontreated group about adhesion degree (p=.645).
Therapy that targets ICAM-1 could be valuable in the management of epidural fibrosis. Blocking the function of ICAM-1 may provide cellular protection against epidural fibrosis and also it may serve as an important component in this period, acting to promote leukocyte migration across epidural area after laminectomy.
其他疾病的研究数据表明细胞黏附分子是纤维化和瘢痕形成的介质。我们试图在动物脊柱手术模型中探索和评估使用抗细胞间黏附分子-1（ICAM-1）及其配体CD-18的单克隆抗体来减少硬膜外纤维化的效果。
我们假设与未治疗组和单克隆抗人免疫球蛋白（Ig）G组相比，使用抗黏附分子（抗ICAM-1和抗CD-18）可减少大鼠脊柱手术后的硬膜外纤维化。
实验性动物脊柱手术（椎板切除术）方案，与单克隆抗人IgG组（作为非特异性单克隆抗体）和未治疗组相比，在试验组的手术部位应用抗黏附分子（抗ICAM-1和抗CD-18组作为特异性单克隆抗体）。
30只体重175至250克的Sprague Dawley雄性或雌性大鼠被随机分为三组（未治疗组、抗ICAM-1和抗CD-18组、单克隆抗人IgG组）。所有动物组均在L4水平进行椎板切除术。注射材料后（未治疗组除外），手术部位分层缝合。三周后，所有大鼠处死。27只大鼠可用于组织学分析。对组织学切片评估椎板切除侧纤维组织中的成纤维细胞数量、硬脑膜与纤维组织之间的粘连程度以及椎板切除区域的新骨形成情况。
比较各组纤维组织中的成纤维细胞数量，抗ICAM-1和抗CD-18组的成纤维细胞数量明显少于未治疗组（p = 0.037）。单克隆抗人IgG组的成纤维细胞数量与抗ICAM-1和抗CD-18组（p = 0.608）以及未治疗组（p = 0.508）无显著差异。在应用抗ICAM-1和抗CD-18的组中，粘连程度在统计学上明显低于单克隆抗人IgG组（p = 0.036）和未治疗组（p = 0.036）。单克隆抗人IgG组和未治疗组之间在粘连程度方面无显著差异（p = 0.645）。
针对ICAM-1的治疗在硬膜外纤维化的管理中可能具有重要价值。阻断ICAM-1的功能可能为防止硬膜外纤维化提供细胞保护，并且它可能在此期间作为一个重要组成部分，在椎板切除术后促进白细胞穿过硬膜外区域迁移。
