Anti-thrombotic activity and safety of nattokinase, an enzyme produced by Bacillus subtilis during soybean fermentation, were investigated in comparison with tissue-type plasminogen activator (t-PA). Carotid arterial thrombosis was produced with a FeCl3-soaked paper, followed by intravenous injection of nattokinase or t-PA. Nattokinase and t-PA delayed thrombus formation, near-fully (> 90%) inhibiting at 75 and 8.5 mg/kg, respectively. As adverse effects, t-PA induced petechial haemorrhage at 10 mg/kg in the lungs and thymus, and extensive bleeding at 20 mg/kg. Nattokinase also caused pulmonary haemorrhage from 300 mg/kg. Collectively, the standard safety margins (SSMs) for t-PA and nattokinase were calculated to be 1.2 and 4.0, respectively. Combinational treatment with dexamethasone (2 mg/kg) increased the efficacy and safety of t-PA and nattokinase, widening their SSMs to 2.4 and 8.0, respectively. The results indicate that nattokinase delayed thrombus formation and dissolved thrombi, and that nattokinase could be a good candidate anti-thrombotic agent with relatively-low haemorrhagic risk.

中文翻译：

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纳豆激酶和组织型纤溶酶原激活剂的比较抗血栓形成活性和出血性不良反应。

与组织型纤溶酶原激活剂（t-PA）相比，研究了纳豆激酶的抗血栓形成活性和安全性，纳豆激酶是枯草芽孢杆菌在大豆发酵过程中产生的酶。用FeCl3浸泡过的纸产生颈动脉血栓形成，然后静脉注射纳豆激酶或t-PA。纳豆激酶和t-PA延迟血栓形成，分别几乎完全（> 90％）分别以75和8.5 mg / kg抑制。作为不良反应，t-PA在肺和胸腺中引起10 mg / kg的瘀斑出血，而在20 mg / kg时引起大量出血。纳豆激酶还引起了300 mg / kg的肺出血。总的来说，t-PA和纳豆激酶的标准安全范围（SSM）分别计算为1.2和4.0。地塞米松（2 mg / kg）的联合治疗可提高t-PA和纳豆激酶的疗效和安全性，将其SSM分别扩大至2.4和8.0。结果表明，纳豆激酶可延迟血栓形成并溶解血栓，并且纳豆激酶可能是出血风险较低的良好抗栓剂。