Medical Laboratory, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China.
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China ; and.
J Cardiovasc Pharmacol. 2024 Oct 1;84(4):440-450. doi: 10.1097/FJC.0000000000001618.
Anticoagulant therapy can significantly reduce the incidence of stroke and peripheral embolism events in patients with atrial fibrillation (AF). Although warfarin is widely used as an anticoagulant drug, a wrong dose can lead to increased risks of bleeding or blood clots. The aim of this study was to assess whether nuclear factor-erythroid-2-related factor 2 (Nrf2) can improve the efficacy of warfarin through the regulation of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) using a rat model of AF. Results showed that AF significantly reduced Nrf2 in myocardial tissue of sham-operated rats. Furthermore, Nrf2 overexpression effectively reduced AF-induced atrial fibrosis by reducing collagen in the left atrium, inhibiting the expression of the fibrosis-related genes collagen I and transforming growth factor-β1 in rats with AF. Nrf2 overexpression can activate CYP2C9, decrease the serum concentration of warfarin, and decrease prothrombin time and international normalized ratio in AF rats. In this article, Nrf2 overexpression protects against fibrosis, increased survival in AF rats, and activated CYP2C9 expression, thus broadening the therapeutic range of warfarin in AF rats.
抗凝治疗可显著降低房颤（AF）患者中风和外周栓塞事件的发生率。虽然华法林被广泛用作抗凝药物，但剂量错误会导致出血或血栓形成的风险增加。本研究旨在评估核因子-红细胞 2 相关因子 2（Nrf2）是否可以通过调节细胞色素 P450 家族 2 亚家族 C 成员 9（CYP2C9），改善 AF 大鼠模型中华法林的疗效。结果表明，AF 显著降低了假手术大鼠心肌组织中的 Nrf2。此外，Nrf2 的过表达通过减少左心房中的胶原，抑制 AF 大鼠中纤维化相关基因胶原 I 和转化生长因子-β1 的表达，有效减少了 AF 引起的心房纤维化。Nrf2 的过表达可以激活 CYP2C9，降低 AF 大鼠中华法林的血清浓度，并降低凝血酶原时间和国际标准化比值。在本文中，Nrf2 的过表达可防止纤维化，增加 AF 大鼠的存活率，并激活 CYP2C9 的表达，从而拓宽了 AF 大鼠中华法林的治疗范围。
