Romecín Paola, Navarro Esther G, Ortiz M Clara, Iyú David, García-Estañ Joaquín, Atucha Noemí M
Department Fisiología, Faculty Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de MurciaMurcia, Spain.
Front Physiol. 2017 Jun 7;8:384. doi: 10.3389/fphys.2017.00384. eCollection 2017.
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model. Cholic acid (CA) or deoxycholic acid (DCA) did not change P-selectin expression or platelet aggregation in any group but elevated baseline platelet calcium levels. Incubation with both bile acids reduced calcium release after stimulation with thrombin in the absence of extracellular calcium. Pretreatment with CA but not with DCA reduced significantly thrombin-induced calcium entry in all three experimental groups. The capacitative calcium entry was also significantly lower in platelets pretreated with both bile acids. The simultaneous addition of thapsigargin and ionomycin to estimate the total amount of calcium in platelet internal stores was decreased by pretreatment with both CA and DCA, although these changes were significantly different in the control rats only with CA and in the BDL platelets with DCA. These results indicate that CA and DCA reduce calcium movements in platelets of control and BDL animals, thus suggesting that bile acids do not participate in the alterations observed in the BDL cirrotic model.
此前，我们发现肝硬化实验模型胆管结扎（BDL）大鼠的血小板内钙稳态发生改变；这些改变与高凝状态的存在相符，且与凝血酶引起的细胞内钙释放增强以及细胞内细胞器中储存的钙量增加有关。在本研究中，我们探究了胆汁酸在BDL肝硬化模型这些改变中的作用。胆酸（CA）或脱氧胆酸（DCA）在任何组中均未改变P-选择素表达或血小板聚集，但提高了血小板基线钙水平。在无细胞外钙的情况下，两种胆汁酸孵育均降低了凝血酶刺激后的钙释放。CA预处理而非DCA预处理在所有三个实验组中均显著降低了凝血酶诱导的钙内流。两种胆汁酸预处理的血小板中钙池调控性钙内流也显著降低。用毒胡萝卜素和离子霉素同时处理以估计血小板内部储存钙的总量，CA和DCA预处理均使其降低，尽管这些变化仅在CA处理的对照大鼠和DCA处理的BDL血小板中存在显著差异。这些结果表明，CA和DCA减少了对照和BDL动物血小板中的钙运动，因此提示胆汁酸不参与BDL肝硬化模型中观察到的改变。
