Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
J Am Coll Cardiol. 2012 Feb 7;59(6):585-92. doi: 10.1016/j.jacc.2011.10.880.
This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF).
Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction. UDCA, a bile acid used in the treatment of cholestatic liver disease, has anti-inflammatory and cytoprotective properties and may contribute to the formation of mixed micelles around lipopolysaccharide. These properties may help to improve peripheral blood flow in patients with CHF.
We performed a prospective, single-center, double-blind, randomized, placebo-controlled crossover study of UDCA in 17 clinically stable male patients with CHF (New York Heart Association functional class II/III, left ventricular ejection fraction <45%). Patients received in random order 500 mg UDCA twice daily for 4 weeks and placebo for another 4 weeks. The primary endpoint was post-ischemic peak peripheral arm blood flow as assessed by strain-gauge plethysmography.
Sixteen patients completed the study. UDCA was well tolerated in all patients. Compared with placebo, UDCA improved peak post-ischemic blood flow in the arm (+18%, p = 0.038), and a trend for improved peak post-ischemic blood flow in the leg was found (+17%, p = 0.079). Liver function improved: compared with placebo, levels of γ-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor α receptor 1 were lower after treatment with UDCA than after placebo (all p < 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor α and interleukin-6 were unchanged or increased compared with placebo.
UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function.
本研究旨在评估熊去氧胆酸（UDCA）对慢性心力衰竭（CHF）患者内皮功能和炎症标志物的影响。
内皮功能障碍在 CHF 患者中很常见，它导致了这种情况下运动能力的限制。细菌脂多糖可能触发促炎细胞因子的释放，并促进进一步的内皮功能障碍。UDCA 是一种用于治疗胆汁淤积性肝病的胆酸，具有抗炎和细胞保护特性，可能有助于在脂多糖周围形成混合胶束。这些特性可能有助于改善 CHF 患者的外周血流。
我们进行了一项前瞻性、单中心、双盲、随机、安慰剂对照的 UDCA 交叉研究，纳入了 17 名临床稳定的男性 CHF 患者（纽约心脏协会功能分级 II/III 级，左心室射血分数 <45%）。患者随机接受 500mg UDCA 每日两次，持续 4 周，然后接受安慰剂治疗 4 周。主要终点是通过应变计体积描记法评估的缺血后峰值外周臂血流。
16 名患者完成了研究。所有患者均耐受良好。与安慰剂相比，UDCA 改善了手臂缺血后的峰值血流（增加 18%，p = 0.038），并且发现腿部缺血后的峰值血流也有改善趋势（增加 17%，p = 0.079）。肝功能改善：与安慰剂相比，使用 UDCA 治疗后，γ-谷氨酰转移酶、天冬氨酸转氨酶和可溶性肿瘤坏死因子α受体 1 的水平均低于安慰剂（均 p < 0.05）。6 分钟步行试验或纽约心脏协会功能分级无变化，与安慰剂相比，肿瘤坏死因子α和白细胞介素-6 的水平不变或增加。
UDCA 在 CHF 患者中耐受良好。UDCA 改善外周血流，并与肝功能改善标志物相关。
