Excessive Plasmin Compromises Hepatic Sinusoidal Vascular Integrity After Acetaminophen Overdose.
Excessive Plasmin Compromises Hepatic Sinusoidal Vascular Integrity After Acetaminophen Overdose.
复制标题
对乙酰氨基酚过量后，过多的纤溶酶会损害肝窦血管的完整性。
DOI：
10.1002/hep.30070
复制
发表时间：
2018
期刊：
影响因子：
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通讯作者：
Griffin,CourtneyT
中科院分区：
文献类型：
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作者：
Gao,Siqi;Silasi-Mansat,Robert;Behar,AmandaR;Lupu,Florea;Griffin,CourtneyT
丝氨酸蛋白酶纤溶酶通过激活基质金属蛋白酶直接和间接降解细胞外基质（ECM）组分。过度的纤溶酶活性和随后的ECM降解导致发育中胚胎的肝窦脆性和出血。我们在这里报告，过度的纤溶酶活性在小鼠对乙酰氨基酚（APAP）过量模型同样损害肝窦血管完整性在成年动物。我们发现，APAP过量后6小时，肝纤溶酶活性显著上调。这种纤溶酶上调先于肝脏血管系统周围的ECM成分纤连蛋白降解和小叶中心窦出血。重要的是，给药的药理纤溶酶抑制剂氨甲环酸或纤溶酶原，纤溶酶的循环酶原，基因减少，改善APAP诱导的肝纤维连接蛋白降解和窦bleeding.Conclusion：这些研究表明，减少纤溶酶稳定APAP过量后肝窦血管的完整性。（肝病学2018; 00：1 - 13）。
The serine protease plasmin degrades extracellular matrix (ECM) components both directly and indirectly through activation of matrix metalloproteinases. Excessive plasmin activity and subsequent ECM degradation cause hepatic sinusoidal fragility and hemorrhage in developing embryos. We report here that excessive plasmin activity in a murine acetaminophen (APAP) overdose model likewise compromises hepatic sinusoidal vascular integrity in adult animals. We found that hepatic plasmin activity is up‐regulated significantly at 6 hours after APAP overdose. This plasmin up‐regulation precedes both degradation of the ECM component fibronectin around liver vasculature and bleeding from centrilobular sinusoids. Importantly, administration of the pharmacological plasmin inhibitor tranexamic acid or genetic reduction of plasminogen, the circulating zymogen of plasmin, ameliorates APAP‐induced hepatic fibronectin degradation and sinusoidal bleeding.Conclusion:These studies demonstrate that reduction of plasmin stabilizes hepatic sinusoidal vascular integrity after APAP overdose. (Hepatology2018; 00:1‐13).