Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
J Thorac Cardiovasc Surg. 2013 Jun;145(6):1611-6, 1616.e1-4. doi: 10.1016/j.jtcvs.2012.11.042. Epub 2013 Jan 16.
Anti-inflammatory effects of tranexamic acid and aprotinin, used to abate perioperative blood loss, are reported and might be of substantial clinical relevance. The study of messenger ribonucleic acid synthesis provides a valuable asset in evaluating the inflammatory pathways involved.
Whole-blood messenger ribonucleic acid expression of 114 inflammatory genes was compared pre- and postoperatively in 35 patients randomized to receive either placebo, tranexamic acid, or aprotinin. These results were further confirmed by reverse transcription-polymerase chain reaction.
Of the 23 genes exhibiting independently altered postoperative gene expression levels, 8 were restricted to the aprotinin group only (growth differentiation factor 3, interleukin 19, interleukin 1 family member 7, transforming growth factor α, tumor necrosis factor superfamily 10, tumor necrosis factor superfamily 12, tumor necrosis factor superfamily 13B, vascular endothelial growth factor α), whereas both aprotinin and tranexamic acid altered gene expression of 3 genes as compared with placebo (FMS-related tyrosine kinase 3 ligand, growth differentiation factor 5, interferon-α8). In general, less upregulation of pro-inflammatory, and more upregulation of anti-inflammatory, genes was observed for patients treated with antifibrinolytics. Gene expression affected by aprotinin coded mostly for proteins that function through serine proteases.
This study demonstrates that the use of tranexamic acid and aprotinin results in altered inflammatory pathways on the genomic expression level. We further demonstrate that the use of aprotinin leads to significant attenuation of the immune response, with several inhibitory effects restricted to the use of aprotinin only. The results aid in a better understanding of the targets of these drugs, and add to the discussion on which antifibrinolytic can best be used in the cardiac surgical patient.
氨甲环酸和抑肽酶可减少围手术期的失血，有抗炎作用，具有重要的临床意义。信使核糖核酸合成的研究为评估相关炎症途径提供了有价值的依据。
35 例随机接受安慰剂、氨甲环酸或抑肽酶的患者，比较术前和术后全血信使核糖核酸表达 114 个炎症基因。通过逆转录-聚合酶链反应进一步证实了这些结果。
在 23 个术后基因表达水平发生独立改变的基因中，有 8 个仅存在于抑肽酶组（生长分化因子 3、白细胞介素 19、白细胞介素 1 家族成员 7、转化生长因子α、肿瘤坏死因子超家族 10、肿瘤坏死因子超家族 12、肿瘤坏死因子超家族 13B、血管内皮生长因子α），而抑肽酶和氨甲环酸与安慰剂相比，分别改变了 3 个基因的基因表达（FMS 相关酪氨酸激酶 3 配体、生长分化因子 5、干扰素-α8）。一般来说，用纤维蛋白溶解抑制剂治疗的患者，促炎基因的上调较少，抗炎基因的上调较多。受抑肽酶影响的基因表达编码的蛋白质主要通过丝氨酸蛋白酶发挥作用。
本研究表明，氨甲环酸和抑肽酶的使用导致基因组表达水平上炎症途径的改变。我们进一步证明，抑肽酶的使用导致免疫反应明显减弱，其中一些抑制作用仅限于抑肽酶的使用。这些结果有助于更好地了解这些药物的作用靶点，并为讨论哪种纤维蛋白溶解抑制剂最适合心脏外科患者提供了依据。
