Buss Armin, Pech Katrin, Kakulas Byron A, Martin Didier, Schoenen Jean, Noth Johannes, Brook Gary A
Department of Neurology, Aachen University Hospital, Aachen, Germany.
BMC Neurol. 2007 Jun 26;7:17. doi: 10.1186/1471-2377-7-17.
Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases that degrade the extracellular matrix and other extracellular proteins. Studies in experimental animals demonstrate that MMPs play a number of roles in the detrimental as well as in the beneficial events after spinal cord injury (SCI). In the present correlative investigation, the expression pattern of several MMPs and their inhibitors has been investigated in the human spinal cord.
An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type.
In the unlesioned human spinal cord, MMP and TIMP immunoreactivity was scarce. After traumatic SCI, a lesion-induced bi-phasic pattern of raised MMP-1 levels could be found with an early up-regulation in macrophages within the lesion epicentre and a later induction in peri-lesional activated astrocytes. There was an early and brief induction of MMP-2 at the lesion core in macrophages. MMP-9 and -12 expression peaked at 24 days after injury and both molecules were mostly expressed in macrophages at the lesion epicentre. Whereas MMP-9 levels rose progressively from 1 week to 3 weeks, there was an isolated peak of MMP-12 expression at 24 days. The post-traumatic distribution of the MMP inhibitors TIMP-1, -2 and -3 was limited. Only occasional TIMP immuno-positive macrophages could be detected at short survival times. The only clear induction was detected for TIMP-3 at survival times of 8 months and 1 year in peri-lesional activated astrocytes.
The involvement of MMP-1, -2, -9 and -12 has been demonstrated in the post-traumatic events after human SCI. With an expression pattern corresponding largely to prior experimental studies, they were mainly expressed during the first weeks after injury and were most likely involved in the destructive inflammatory events of protein breakdown and phagocytosis carried out by infiltrating neutrophils and macrophages, as well as being involved in enhanced permeability of the blood spinal cord barrier. Similar to animal investigations, the strong induction of MMPs was not accompanied by an expression of their inhibitors, allowing these proteins to exert their effects in the lesioned spinal cord.
基质金属蛋白酶（MMPs）是一类细胞外肽酶家族，可降解细胞外基质和其他细胞外蛋白质。对实验动物的研究表明，MMPs在脊髓损伤（SCI）后的有害和有益事件中都发挥着多种作用。在本次相关性研究中，已对几种MMPs及其抑制剂在人类脊髓中的表达模式进行了研究。
对对照和损伤的人类脊髓尸检样本进行免疫组织化学研究。所有创伤性SCI患者经临床诊断为“完全性”损伤，并呈现出浸渍型损伤。
在未损伤的人类脊髓中，MMP和TIMP免疫反应性稀少。创伤性SCI后，可发现损伤诱导的MMP-1水平呈双相模式升高，早期在损伤中心的巨噬细胞中上调，后期在损伤周围活化的星形胶质细胞中诱导。MMP-2在损伤核心的巨噬细胞中有早期且短暂的诱导。MMP-9和-12的表达在损伤后24天达到峰值，且这两种分子主要在损伤中心的巨噬细胞中表达。MMP-9水平从1周逐渐升高至3周，而MMP-12的表达在24天出现单独的峰值。MMP抑制剂TIMP-1、-2和-3的创伤后分布有限。在短存活时间内仅偶尔能检测到TIMP免疫阳性巨噬细胞。在8个月和1年的存活时间，仅在损伤周围活化的星形胶质细胞中检测到TIMP-3的明显诱导。
已证明MMP-1、-2、-9和-12参与人类SCI后的创伤后事件。其表达模式在很大程度上与先前的实验研究一致，它们主要在损伤后的最初几周表达，很可能参与了由浸润的中性粒细胞和巨噬细胞进行的蛋白质分解和吞噬等破坏性炎症事件，以及血脊髓屏障通透性增强。与动物研究相似，MMPs的强烈诱导并未伴随着其抑制剂的表达，使得这些蛋白质能够在损伤的脊髓中发挥作用。
