不同剂量非布司他对痛风伴高尿酸血症的效果及对内皮素-1水平的影响

Impact of Different Doses of Febuxostat on Uric Acid and Endothelin-1 Level in Patients with Gout and Hyperuricemia

目的对比分析不同剂量非布司他与别嘌呤醇对痛风伴高尿酸血症的效果及其对血管内皮素-1(ET-1)水平的影响。方法选取2010年6—10月在我院门诊就诊的60例痛风伴高尿酸血症患者,随机分为3组,分别给予非布司他40 mg/d(A1组)、非布司他80 mg/d(A2组)和别嘌呤醇300 mg/d(A3组),疗程均为24周,分别测定治疗前及治疗12、24周后血尿酸和ET-1的水平。结果 3组治疗12、24周后血尿酸和ET-1水平均较治疗前下降(P<0.05),但治疗12、24周后,3组血尿酸和ET-1水平间差异无统计学意义(P>0.05)。相关分析显示,收缩压(SBP)、舒张压(DBP)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)与ET-1无线性相关性(r=-0.074、0.016、-0.073、0.062,P=0.397、0.858、0.401、0.477),尿素氮(BUN)、肌酐(Cr)与ET-1呈负相关(r=-0.205、-0.190,P=0.017、0.028),血尿酸与ET-1呈正相关(r=0.461,P=0.000)。结论非布司他、别嘌呤醇均可明显降低痛风伴高尿酸血症患者的血尿酸水平,改善患者血管内皮细胞功能,但较大剂量的非布司他对ET-1的降低作用有待进一步研究。

Objective To explore the impact of Febuxostat and allopurinol on uric acid and endothelin - 1 （ ET - 1 ） level in patients with gout and hyperuricemia. Methods Totally 60 outpatients with gout and hyperuricemia treated in our hospi- tal between June and October in 2010 were included in our study. They were randomly divided into three groups, and each group was given Febuxostat 40 mg/d （ group A1 ） , Febuxostat 80 mg/d （ group A2） , or allopurinol 300 mg/d （ group A3 ） for 24 weeks. The levels of uric acid and ET - 1 were measured at 0, 12, and 24 week. Results The levels of uric acid and ET - 1 in the three groups were all declined significantly after 12 weeks and 24 weeks of treatment （P 〈 0. 05 ）, and there was no statisti- cal difference in the levels of uric acid and ET - 1 at 12 weeks and 24 weeks in the three groups. The correlation analysis showed that there was no linear correlation between systolic blood pressure, diastolic blood pressure, alanine aminotransferase, and as- partate transaminase and ET - 1 （r = -0. 074, 0. 016, -0. 073, 0. 062 ; P = 0. 397, 0. 858, 0. 401, 0. 477）. But the lev- el of ET - 1 was negatively correlated with urea nitrogen and creatinine （ r = - 0. 205, P = 0. 017 ; r = - 0. 190, P = 0. 028 ） , and positively correlated with uric acid （ r = 0. 461, P = 0. 000）. Conclusion Febuxostat and allopurinol could reduce the lev- el of uric acid and improve the function of endothelial cells. Further investigation is still needed to clarify the mechanism of large - dose Febuxostat in reducing ET - 1 level.