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Role of homocysteine and folic acid on the altered calcium homeostasis of platelets from rats with biliary cirrhosis

机译:同型半胱氨酸和叶酸对胆汁肝硬化大鼠血小板钙稳态的作用

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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. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombin-induced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.
机译:以前,我们发现从肝硬化的实验模型中,细胞内钙稳态在血小板中改变,胆管连接(BDL)大鼠;这些改变与超可凝固状态的存在兼容。不同的研究表明,胆汁淤积疾病与高胱氨酸血症有关;因此,我们假设它可能有助于这些血小板改变。在本研究中,我们研究了在BDL模型中的血小板聚集和钙信号传导中的同颗粒(HCY)的作用。还分析了慢性叶酸处理的作用。急性治疗Hcy增加了对照和BDL大鼠血小板中ADP和钙响应的聚集反应。 Hcy没有改变电容钙入口。叶酸中的慢性处理降低了对照和BDL大鼠的血小板聚集,但在BDL大鼠中这种降低更大。在叶酸处理的大鼠中,对照大鼠的血小板中血栓诱导的钙入口和释放减少,但在BDL大鼠中毫不替换;然而,在用叶酸处理的对照组和BDL大鼠的血小板中降低了电容性钙入口。在用Hcy或凝血酶的刺激和叶酸标准化这些反应后,通过BDL血小板在较高水平下产生反应性氧物质。 Hcy在增强BDL大鼠的血小板聚集响应中起作用,可能是通过增强的ROS形成。叶酸预处理标准化BDL大鼠所示的许多血小板改变。

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