Smirnova I V, Salazar A, Arnold P M, Glatt S, Handler M, Festoff B W
Neurobiology Research Laboratory, Department of Veterans Affairs Medical Center, Kansas City, MO 64128, USA.
Thromb Haemost. 1997 Dec;78(6):1473-9.
The blood coagulation cascade proteolytic enzyme, thrombin, affects many cell types, including neurons and astrocytes, in which it prevents process outgrowth and induces significant morphological degeneration and even cell death. Since thrombin may contribute significantly to pathological conditions in the central nervous system (CNS), where it is synthesized locally, we measured the levels of thrombin and its precursor, prothrombin, in the cerebrospinal fluid (CSF) of 67 individuals from 6 groups: non-neurologic controls (NNC); spinal degenerative disease (SDD); peripheral nerve disease (PND); cerebrovascular, neuroimmune and seizure disorders and tumor (CNSD); traumatic brain injury (TBI) and neurodegenerative disorders (NDD). We employed a sensitive chromogenic assay utilizing the thrombin specific tripeptide substrate, S-2238, to evaluate CSF levels of thrombin and prothrombin. The latter estimated after its conversion to active enzyme by the snake venom prothrombinase, ecarin. No measurable active thrombin was detected in these CSF samples. However, activatable prothrombin was measured in all groups. The mean activatable prothrombin concentrations (in nM) were 7.26 +/- 3.39 (NNC); 8.85 +/- 3.09 (SDD); 6.78 +/- 2.58 (PND); 6.33 +/- 3.87 (CNSD); 5.10 +/- 1.86 (TBI), and 7.80 +/- 3.27 (NDD). Duncan's multiple comparison test showed significant reduction (p <0.05) in prothrombin levels of the TBI group. Our data suggests that the prothrombin zymogen gains access to the CSF, likely across either an intact or compromised blood-brain barrier (BBB), in increased amounts with age. Reduced levels in TBI patients may have diagnostic and/or prognostic value.
血液凝固级联反应中的蛋白水解酶凝血酶会影响多种细胞类型，包括神经元和星形胶质细胞，它会抑制细胞突起生长，导致显著的形态学退变甚至细胞死亡。由于凝血酶可能在中枢神经系统（CNS）的病理状况中起重要作用，而中枢神经系统中凝血酶是在局部合成的，我们测量了来自6组的67名个体脑脊液（CSF）中凝血酶及其前体凝血酶原的水平：非神经学对照（NNC）；脊柱退行性疾病（SDD）；周围神经疾病（PND）；脑血管、神经免疫和癫痫疾病及肿瘤（CNSD）；创伤性脑损伤（TBI）和神经退行性疾病（NDD）。我们采用一种利用凝血酶特异性三肽底物S-2238的灵敏显色测定法来评估脑脊液中凝血酶和凝血酶原的水平。后者是在通过蛇毒凝血酶原激活剂依卡瑞将其转化为活性酶后进行估算的。在这些脑脊液样本中未检测到可测量的活性凝血酶。然而，在所有组中都检测到了可激活的凝血酶原。可激活凝血酶原的平均浓度（以nM计）分别为：7.26±3.39（NNC）；8.85±3.09（SDD）；6.78±2.58（PND）；6.33±3.87（CNSD）；5.10±1.86（TBI），以及7.80±3.27（NDD）。邓肯多重比较检验显示TBI组的凝血酶原水平显著降低（p<0.05）。我们的数据表明，凝血酶原酶原可能通过完整或受损的血脑屏障（BBB）进入脑脊液，其含量会随着年龄增长而增加。TBI患者中凝血酶原水平降低可能具有诊断和/或预后价值。
