Martínez-Torres Francisco J, Wagner Simone, Haas Jürgen, Kehm Roland, Sellner Johann, Hacke Werner, Meyding-Lamadé Uta
Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Neurosci Lett. 2004 Sep 30;368(3):274-8. doi: 10.1016/j.neulet.2004.06.064.
Herpes simplex virus encephalitis (HSVE) causes elevated morbidity and mortality despite antiviral treatment. Virus-independent mechanisms may perpetuate brain damage. Matrix metalloproteinases (MMPs) target extracellular matrix components. This study describes the protein and mRNA expression of MMP2 and MMP9 in experimental HSVE in the short and long term. Ten SJL-NBOM mice were infected with neurovirulent HSV-1 and compared with nine controls. The presence of MMP2 and MMP9 in brain tissue was analyzed with sodium-dodecyl-sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gelatin zymography and mRNA expression of MMP2 and MMP9 with quantitative real-time PCR at days 7, 21 and 180 post-inoculation. Infected animals had a significantly elevated gelatinolytic activity of MMP2 at all time points, and of MMP9 at days 21 and 180. Increased presence of MMP2 and MMP9 in chronic HSVE may contribute to ongoing damage. Inhibition of MMP2 and MMP9 might be a suitable target for therapeutic intervention.
尽管进行了抗病毒治疗，单纯疱疹病毒性脑炎（HSVE）仍会导致发病率和死亡率升高。与病毒无关的机制可能会使脑损伤持续存在。基质金属蛋白酶（MMPs）作用于细胞外基质成分。本研究描述了MMP2和MMP9在实验性HSVE短期和长期中的蛋白质及mRNA表达情况。将10只SJL-NBOM小鼠感染神经毒性HSV-1，并与9只对照小鼠进行比较。在接种后第7天、21天和180天，采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）明胶酶谱法分析脑组织中MMP2和MMP9的存在情况，并用定量实时PCR分析MMP2和MMP9的mRNA表达。感染动物在所有时间点的MMP2明胶酶解活性均显著升高，在第21天和180天MMP9的明胶酶解活性也显著升高。慢性HSVE中MMP2和MMP9的存在增加可能会导致持续性损伤。抑制MMP2和MMP9可能是治疗干预的合适靶点。
