Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Circulation. 2012 Jul 31;126(5):598-603. doi: 10.1161/CIRCULATIONAHA.112.105775. Epub 2012 Jul 6.
Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors.
A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 versus 9.4±2.7 μmol/L; P<0.001). Serum concentrations of malondialdehyde-modified low-density lipoprotein and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8±24.5 versus 72.5±21.8 U/L, P=0.034; 7.8±2.4 versus 10.4±3.2 ng/mg creatinine, P=0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2±2.2% versus 5.9±1.7%; P<0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin (r=0.44, P<0.001), malondialdehyde-modified low-density lipoprotein (r=-0.25, P=0.01), and urinary excretion of 8-OHdG (r=-0.27, P=0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with malondialdehyde-modified low-density lipoprotein (r=-0.20, P=0.04) and 8-OHdG (r=-0.21, P=0.02) in patients with Gilbert syndrome but not in control subjects.
Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation.
URL: http://www.umin.ac.jp. Unique identifier: UMIN000003409.
吉尔伯特综合征患者有轻度未结合高胆红素血症。已有研究表明胆红素是一种内源性抗氧化剂。我们评估了在无心血管危险因素的情况下，正常条件下吉尔伯特综合征患者的氧化应激对内皮功能的作用。
本研究共纳入 108 例无心血管危险因素的年轻男性吉尔伯特综合征患者和 108 例年龄匹配的健康男性（正常对照组）。与对照组相比，吉尔伯特综合征患者的血清胆红素浓度更高（29.2±11.6 与 9.4±2.7 μmol/L；P<0.001）。血清丙二醛修饰的低密度脂蛋白和 8-羟基-2'-脱氧鸟苷（8-OHdG）的尿排泄量（氧化应激的指标）在吉尔伯特综合征患者中低于对照组（61.8±24.5 与 72.5±21.8 U/L，P=0.034；7.8±2.4 与 10.4±3.2 ng/mg 肌酐，P=0.001）。与正常对照组相比，吉尔伯特综合征患者的血流介导的血管扩张更大（7.2±2.2%与 5.9±1.7%；P<0.001）。两组之间对硝化甘油的血管反应没有显著差异。在吉尔伯特综合征患者中，血流介导的血管扩张与血清胆红素浓度（r=0.44，P<0.001）、丙二醛修饰的低密度脂蛋白（r=-0.25，P=0.01）和 8-OHdG 尿排泄量（r=-0.27，P=0.004）相关，但在对照组中没有。此外，在吉尔伯特综合征患者中，血清胆红素浓度与丙二醛修饰的低密度脂蛋白（r=-0.20，P=0.04）和 8-OHdG（r=-0.21，P=0.02）相关，但在对照组中没有。
吉尔伯特综合征患者的氧化应激水平较低，与高胆红素血症相关，并增强了内皮依赖性血管舒张。
