Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
Neuropathol Appl Neurobiol. 2011 Aug;37(5):525-37. doi: 10.1111/j.1365-2990.2010.01157.x.
3-Nitropropionic acid (3-NPA) is a natural toxin that, when administered to experimental animals, reproduces the brain lesions observed in Huntington's disease, which mainly consist of selective neurodegeneration of the striatum. The lesions also include severe alterations to the blood-brain barrier (BBB), which increase its permeability to several substances including blood components and exogenous fluorescent dyes, and the concomitant degradation of some of its constituents such as endothelial cells, tight junction proteins and the basement membrane. We studied here the role of matrix metalloproteinases (MMPs)-2 and -9, also called gelatinases A and B, in the degradation of the BBB in the striatal lesions induced by the systemic administration of 3-NPA to Sprague-Dawley rats.
3-NPA was intraperitoneally administered at a dose of 20 mg/kg once a day for 3 days. MMPs were studied by means of immunohistochemistry and in situ zymography.
In 3-NPA-treated rats, MMP-9 was present in most of the degraded blood vessels in the injured striatum, while it was absent in vessels from non-injured tissue. In the same animals, MMP-2 staining was barely detected close to degraded blood vessels. The combination of MMP-9 immunostaining, in situ zymography and inhibitory studies of MMP-9 confirmed that net gelatinolytic activity detected in the degraded striatal blood vessels could be attributed almost exclusively to the active form of MMP-9.
Our results highlight the prominent role of MMP-9 in BBB disruption in the striatal injured areas of this experimental model of Huntington's disease.
3-硝基丙酸（3-NPA）是一种天然毒素，当给实验动物施用时，会复制亨廷顿病中观察到的脑损伤，主要包括纹状体的选择性神经退行性变。病变还包括血脑屏障（BBB）的严重改变，这会增加其对包括血液成分和外源性荧光染料在内的几种物质的通透性，并且同时降解其一些成分，如内皮细胞、紧密连接蛋白和基膜。我们在这里研究了基质金属蛋白酶（MMPs）-2 和 -9，也称为明胶酶 A 和 B，在 3-NPA 系统给药诱导的纹状体损伤中 BBB 降解中的作用。
3-NPA 以 20mg/kg 的剂量每天腹膜内注射一次，连续 3 天。通过免疫组织化学和原位酶谱法研究 MMPs。
在 3-NPA 处理的大鼠中，MMP-9 存在于损伤纹状体中大多数降解的血管中，而在未受损组织的血管中不存在。在相同的动物中，MMP-2 染色在靠近降解的血管处几乎检测不到。MMP-9 免疫染色、原位酶谱法和 MMP-9 抑制研究的组合证实，在降解的纹状体血管中检测到的净明胶酶活性几乎可以完全归因于 MMP-9 的活性形式。
我们的结果强调了 MMP-9 在这种亨廷顿病实验模型的纹状体损伤区域中 BBB 破坏中的突出作用。
