Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
PLoS One. 2014 Jun 3;9(6):e98513. doi: 10.1371/journal.pone.0098513. eCollection 2014.
The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca(2+)). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.
乙酰水杨酸（ASP）的使用受到其不良反应的限制，特别是对胃黏膜的影响。为了解决这个问题，我们合成了 ASP 的一种衍生物，通过用纳米羟基磷灰石（一种含有 Ca(2+)的无机颗粒）修饰 ASP 来制备。该衍生物被命名为 Ca-ASP。结构研究表明，Ca-ASP 是一种含有分子内氢键的羧酸盐。给予大鼠高剂量的 Ca-ASP（5mmol/kg 体重）表现出与给予相同剂量 ASP 相似的抗血栓活性，但对胃黏膜的损伤明显低于 ASP（UI：2 比 UI：12.5）。这些大鼠还表现出 COX-2 表达减少，但 COX-1 表达与对照组大鼠相似，但明显高于给予 ASP 的大鼠。此外，与给予 ASP 的大鼠相比，给予 Ca-ASP 的大鼠前列腺素 E2（PGE2）水平上调。综上所述，结果表明 Ca-ASP 具有与 ASP 相似的抗血栓活性，但没有与 ASP 相关的副作用，其潜在机制可能集中在抑制 COX-2 而不抑制 COX-1，从而有利于 PGE2 的产生，PGE2 在抑制血小板聚集和血栓形成以及胃损伤修复中起着至关重要的作用。
