Neutral proteases and disruption of the blood-brain barrier in rat
Neutral proteases and disruption of the blood-brain barrier in rat
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DOI：
10.1016/s0006-8993(97)00567-2
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发表时间：
1997-09-05
期刊：
影响因子：
2.9
通讯作者：
Rosenberg, GA
中科院分区：
文献类型：
--
作者：
Armao, D;Kornfeld, M;Rosenberg, GA
血脑屏障破坏在许多神经系统疾病中很常见。基质金属蛋白酶在脑损伤中被诱导，通过攻击脑毛细血管周围的细胞外基质增加毛细血管通透性。其他中性蛋白酶在继发性损伤部位也增加，可能有助于血脑屏障的蛋白水解。因此，我们研究了脑内注射中性粒细胞弹性酶、组织蛋白酶G、肝素酶和纤溶酶后毛细血管通透性和组织学组织损伤。成年大鼠脑内注射一种酶。在1、4或24小时后，测量大脑对放射性标记示踪剂[C-14]蔗糖的摄取。将显著增加毛细血管通透性的酶注射到其他大鼠体内，对组织损伤进行组织学评估。与对照组相比，弹性蛋白酶显著增加了毛细血管渗透率；在第4小时，纤溶酶的通透性增加幅度较小，在第24小时对蔗糖摄取的影响最大。组织蛋白酶G在第4小时的影响很小，肝素酶没有影响。弹性酶注射后24小时的脑组织组织学检查显示多灶性血管周围和肺实质内急性出血伴多形核细胞浸润。弹性酶注射脑在显微镜下与盐水注射脑在1和4小时相似。纤溶酶在24小时血管中产生纤维蛋白样变化，与毛细血管通透性的最大增加相一致。我们得出结论，中性粒细胞弹性蛋白酶攻击毛细血管细胞外基质，引起广泛出血，而纤溶蛋白导致血管通透性增加和血管壁纤维蛋白样坏死。损伤后释放的中性蛋白酶的不同作用可能在血管通透性的急性改变和血管结构的长期改变中都很重要。(C) 1997爱思唯尔科学有限公司
Blood-brain barrier disruption is common in many neurological diseases. Matrix metalloproteinases are induced in brain injury and increase capillary permeability by attacking the extracellular matrix around cerebral capillaries. Other neutral proteases are also increased in sites of secondary injury, and may contribute to the proteolysis of the blood-brain barrier. Therefore, we studied capillary permeability and histological tissue damage after intracerebral injection of neutrophil elastase, cathepsin G, heparatinase and plasmin. Adult rats were injected intracerebrally with an enzyme. After 1, 4 or 24 h, measurements were made of brain uptake of a radiolabeled tracer, [C-14]sucrose. Enzymes that significantly increased capillary permeability were injected into other rats for histological assessment of tissue damage. Elastase increased capillary permeability significantly when compared with controls; maximal damage was seen at 4 h. Plasmin produced smaller increases in permeability at 4 h, exerting its maximal effect on sucrose uptake at 24 h. Cathepsin G had a small effect at 4 h. Heparitinase had no effect. Histologic examination of elastase-injected brains at 24 h revealed multifocal perivascular and intraparenchymal acute hemorrhages accompanied by a polymorphonuclear cell infiltrate. Elastase-injected brains were microscopically similar to saline-injected brains at 1 and 4 h. Plasmin produced fibrinoid changes in the blood vessels at 24 h, coinciding with the maximal increase in capillary permeability. We conclude that neutrophil elastase attacks the capillary extracellular matrix, causing extensive hemorrhage, while plasmin leads to increased vascular permeability and fibrinoid necrosis of blood vessel walls. Differential effects of neutral proteases released secondary to injury could be important in both the acute changes in blood vessel permeability and long-term alterations in vessel structure. (C) 1997 Elsevier Science B.V.