Department of Clinical Pharmacy and Healthcare Science, Faculty of Pharmacy, Institute of Medical, Pharmaceutical & Health Science, Kanazawa University, Kanazawa, Japan;
Department of Clinical Pharmacy and Healthcare Science, Faculty of Pharmacy, Institute of Medical, Pharmaceutical & Health Science, Kanazawa University, Kanazawa, Japan.
In Vivo. 2021 Jul-Aug;35(4):1999-2004. doi: 10.21873/invivo.12468.
BACKGROUND/AIM: We examined the mechanism of nitric oxide (NO) production in a tissue-factor (TF)-induced disseminated intravascular coagulation (DIC) model in rats, using inducible nitric oxide synthase (iNOS) inhibitor (L-NIL), endothelial nitric oxide synthase (eNOS) inhibitor (L-NAME), Factor Xa inhibitor (DX-9065a), and thrombin inhibitor argatroban.
Experimental DIC was induced by sustained infusion of 3.75 U/kg TF for 4 h via the tail vein. We then investigated the effect of these four agents on TF-induced DIC.
Administration of L-NIL or L-NAME during induction of TF-induced DIC did not affect hemostatic markers, whereas elevated plasma levels of NO metabolites (NOX) were significantly suppressed by co-administration of L-NAME. A significant increase in eNOS-mRNA expression was observed in the TF-induced DIC model. Argatroban almost completely suppressed eNOS-mRNA expression.
eNOS plays an important role in the NO production in the TF-induced DIC, and thrombin is a key stimulant of eNOS-mRNA expression in this model.
背景/目的：我们使用诱导型一氧化氮合酶（iNOS）抑制剂（L-NIL）、内皮型一氧化氮合酶（eNOS）抑制剂（L-NAME）、Xa 因子抑制剂（DX-9065a）和凝血酶抑制剂 argatroban，研究了组织因子（TF）诱导的弥散性血管内凝血（DIC）模型中一氧化氮（NO）产生的机制。
通过尾静脉持续输注 3.75 U/kg TF 4 小时诱导实验性 DIC。然后，我们研究了这四种药物对 TF 诱导的 DIC 的影响。
在诱导 TF 诱导的 DIC 期间给予 L-NIL 或 L-NAME 不会影响止血标志物，而联合给予 L-NAME 可显著抑制 NO 代谢物（NOX）的血浆水平升高。在 TF 诱导的 DIC 模型中观察到 eNOS-mRNA 表达显著增加。argatroban 几乎完全抑制了 eNOS-mRNA 的表达。
eNOS 在 TF 诱导的 DIC 中 NO 的产生中起重要作用，而凝血酶是该模型中 eNOS-mRNA 表达的关键刺激物。
