摘要
目的评估非布司他对无症状高尿酸血症患者血管内皮功能、颈总动脉内中膜厚度(C-IMT)和弹性的影响。方法本研究为随机对照临床研究,纳入2018年10月至2020年10月淮安市第一人民医院门诊和住院的无症状高尿酸血症患者,随机分为非布司他组和对照组两组,分别在基线和治疗1、3和6个月检测两组患者血清尿酸(UA)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)、空腹胰岛素(FINS)、一氧化氮(NO)、内皮素-1(ET-1)、丙二醛(MDA)和超氧化物歧化酶(SOD)水平,彩超定量肱动脉血流介导的血管扩张功能(FMD);在基线和治疗12个月时检测颈总动脉以下参数:C-IMT、顺应性(AC)、脉搏波传导速度(PWVβ)、僵硬度(β)和压力应变弹性系数(Ep)。比较治疗前后及两组之间的差异。通过Pearson相关分析非布司他治疗12个月与基线的差值ΔUA与ΔNO、ΔET-1、ΔC-IMT、ΔAC、Δβ、ΔEp和ΔPWVβ的相关性。结果非布司他治疗3个月后TG和稳态模型评估的胰岛素抵抗指数(HOMA-IR)较基线下降;反映血管内皮功能的指标FMD和血清NO浓度较基线升高,ET-1较基线下降;氧化应激指标SOD较基线升高,MDA较基线下降。治疗12个月后C-IMT较基线无明显变化,AC较基线升高,PWVβ和β较基线下降,Ep较基线无明显变化。非布司他治疗6个月后ΔFMD与ΔUA负相关(r=-0.403,P=0.004),ΔNO与ΔUA(r=-0.187,P=0.194)、ΔET-1与ΔUA(r=0.038,P=0.791)无相关性,ΔUA是ΔFMD的独立影响因素(F=2.94,P=0.003,调整后R2=0.139)。治疗12个月后ΔAC与ΔUA负相关(r=-0.333,P=0.018),ΔPWVβ与ΔUA正相关(r=0.305,P=0.031),ΔC-IMT与ΔUA(r=0.169,P=0.240)、Δβ与ΔUA(r=-0.214,P=0.136)、ΔEp与ΔUA(r=-0.077,P=0.597)无明显相关性。对照组以上指标在各随访时间点与基线相比差异均无统计学意义。结论非布司他能改善无症状高尿酸血症患者的血管内皮功能和弹性,这种作用可能与非布司他降低氧化应激反应有关。
Objective To evaluate the effect of febutostat on vascular endothelial function,intima-media thickness(C-IMT)and elasticity of the carotid artery in patients with asymptomatic hyperuricemia.Methods This study was a randomized controlled clinical trial that enrolled asymptomatic hyperuricemia patients from the outpatient and inpatient departments of Huai′an First People′s Hospital from October 2018 to October 2020.The participants were randomly divided into two groups:the Febuxostat group and the control group.Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),fasting blood glucose(FBG),fasting insulin(FINS),nitric oxide(NO),endothelin-1(ET-1),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured at baseline and 1,3,and 6 months after treatment,and brachial artery flow-mediated dilation(FMD)was quantified by color Doppler ultrasound.The following parameters of the common carotid artery were detected at baseline and 12 months after treatment:C-IMT,arterial compliance(AC),one-point pulse wave velocity(PWV),stiffness index(β),and pressure-strain elasticity modulus(Ep).The differences before and after treatment and between the two groups were compared.Pearson correlation was used to analyze the correlation betweenΔUA andΔNO,ΔET-1,ΔC-IMT,ΔAC,Δβ,ΔEp,andΔPWVβafter treatment with febuxostat.Results Compared with baseline,TG,HOMA-IR,ET-1 and MDA were significantly lower,while FMD,NO and SOD were significantly higher after 3-months treatment with febuxostat.After 12-months treatment,there was no significant difference in C-IMT or Ep,but there was an increase in AC and a decrease in PWVβorβcompared with baseline.There was a negative correlation betweenΔFMD andΔUA(r=-0.403,P=0.004),but there were no correlations betweenΔNO andΔUA(r=-0.187,P=0.194),ΔET-1 andΔUA(r=0.038,P=0.791)after 6-months treatment.AndΔUA was an independent factor forΔFMD(F=2.94,P=0.003,adjusted R2=0.139).After 12-months treatment,there was a negative correlation betweenΔAC andΔUA,and a positive correlation betweenΔPWVβandΔUA,but there were no correlations between the following indicators:ΔC-IMT andΔUA(r=0.169,P=0.240),ΔβandΔUA(r=-0.214,P=0.136),ΔEp andΔUA(r=-0.077,P=0.597).In the control group,there were no differences among the above indicators between each follow-up time and baseline.Conclusion Febuxostat improves vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia,which may be related to the decreased oxidative stress response.
作者
董美娟
毛莉
张卉新
安坤
Dong Meijuan;Mao Li;Zhang Huixin;An Kun(Department of Ultrasound,the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University,Huaian 223300,China;Department of Neurology,the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University,Huaian 223300,China)
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2023年第8期667-675,共9页
Chinese Journal of Endocrinology and Metabolism
关键词
非布司他
无症状性高尿酸血症
内皮功能
血管弹性
Febuxostat
Asymptomatic hyperuricemia
Endothelial function
Vascular elasticity
