Nath R K, Kwon B, Mackinnon S E, Jensen J N, Reznik S, Boutros S
Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Plast Reconstr Surg. 1998 Sep;102(4):1100-6; discussion 1107-8.
Epineurial scarring in peripheral nerve after injury inhibits normal axonal regeneration primarily due to fibroblast deposition of type I collagen. The transforming growth factor beta (TGF-beta) family is an important class of signaling molecules that has been shown to stimulate fibroblasts to produce collagen. The aim of this study was to design a prototypic therapeutic system in which the neutralization of TGF-beta in crushed rat sciatic nerve would decrease collagen formation. A total of 45 experimental Lewis rats were used. Group 1 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate buffer solution. Group 2 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate-buffered saline and goat, anti-rat, panspecific TGF-beta antibody. Group 3 control animals (five rats) underwent only exposure of sciatic nerve with injection of antibody. All animals were killed at 14 days and sciatic nerve specimens were harvested at that time. Slides of experimental tissue were processed using a 35S-labeled oligomer for procollagen alpha-1 mRNA, then dipped in photographic emulsion and examined by darkfield autoradiography. Morphometric analysis of pixel counts was then performed. A significant reduction in total pixel count per high-power field and in total number of fibroblasts per high-power field was found in crushed rat sciatic nerve treated with anti-TGF-beta antibody when compared with those treated only with phosphate-buffered saline. These findings are consistent with successful reduction in procollagen induction after a crush injury by topical administration of blocking antibody against transforming growth factor beta. The concept of growth factor blockade for therapeutic collagen reduction is attractive in the context of nerve injury, and the current article provides a model for future clinical application.
损伤后周围神经的神经外膜瘢痕形成主要由于成纤维细胞沉积I型胶原，从而抑制正常轴突再生。转化生长因子β（TGF-β）家族是一类重要的信号分子，已被证明可刺激成纤维细胞产生胶原。本研究的目的是设计一种原型治疗系统，在大鼠坐骨神经挤压伤中中和TGF-β可减少胶原形成。总共使用了45只实验性Lewis大鼠。第1组动物（20只大鼠）坐骨神经遭受单侧挤压伤并注射磷酸盐缓冲溶液。第2组动物（20只大鼠）坐骨神经遭受单侧挤压伤并注射磷酸盐缓冲盐水和山羊抗大鼠全特异性TGF-β抗体。第3组对照动物（5只大鼠）仅暴露坐骨神经并注射抗体。所有动物在14天时处死，并在此时采集坐骨神经标本。实验组织切片用35S标记的前胶原α-1 mRNA寡聚物处理，然后浸入照相乳剂中，通过暗视野放射自显影检查。然后进行像素计数的形态计量分析。与仅用磷酸盐缓冲盐水处理的大鼠坐骨神经挤压伤相比，用抗TGF-β抗体处理的大鼠坐骨神经挤压伤中，每个高倍视野的总像素计数和每个高倍视野的成纤维细胞总数显著减少。这些发现与通过局部施用抗转化生长因子β阻断抗体成功减少挤压伤后前胶原诱导一致。在神经损伤的背景下，生长因子阻断以减少治疗性胶原的概念很有吸引力，本文提供了一个未来临床应用的模型。
