Department of Structure and function of proteins, Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine.
National University of Life and Environmental Sciences of Ukraine, Kyiv, Ukraine.
Animal Model Exp Med. 2023 Feb;6(1):66-73. doi: 10.1002/ame2.12301. Epub 2022 Dec 27.
Knowing the variability of blood coagulation responses to liver damage of different origins can provide a key to curing liver tissues or to mitigating treatment side effects. The aim of the present work was to compare the changes in the main components of hemostasis under experimental drug-induced hepatosis and hepatitis in rats.
We modeled diclofenac-induced hepatitis and tetracycline-induced hepatosis. Hemostasis response was gauged by measuring fibrinogen, factor X, protein C (PC), and prothrombin in plasma. The decarboxylated form of prothrombin was detected by measuring prothrombin index and ecamulin index. Platelet reactivity was studied using aggregometry.
Both hepatitis and hepatosis decreased the synthesis of fibrinogen, factor X, and prothrombin. However, protein carboxylation was not disrupted in hepatosis but was much impaired in hepatitis. PC decreased in both models as a consequence of its consumption possibly during inflammatory response. Platelet aggregation rate was lower in hepatosis but higher in hepatitis.
Our findings imply the need for a thorough monitoring of the hemostasis system in liver diseases to avoid possible thrombotic complications. Its state indicates the disorder's rate and character.
了解不同来源的肝损伤对凝血反应的变化差异，可为治疗肝组织或减轻治疗副作用提供关键信息。本研究旨在比较实验性药物诱导的肝炎和大鼠肝损伤时止血系统主要成分的变化。
我们建立了双氯芬酸诱导的肝炎和四环素诱导的肝损伤模型。通过测量血浆中的纤维蛋白原、因子 X、蛋白 C（PC）和凝血酶原来评估止血反应。通过测量凝血酶原指数和 ecamulin 指数来检测凝血酶原的脱羧形式。使用聚集仪研究血小板反应性。
肝炎和肝损伤均降低了纤维蛋白原、因子 X 和凝血酶原的合成。然而，肝损伤并未破坏蛋白的羧化作用，而肝炎则严重损害了蛋白的羧化作用。可能是由于炎症反应，两种模型中的 PC 均减少。肝损伤时血小板聚集率较低，而肝炎时则较高。
我们的研究结果表明，需要对肝脏疾病中的止血系统进行全面监测，以避免可能的血栓并发症。其状态表明了疾病的速度和特征。
