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《工程(英文)》 >> 2022年 第16卷 第9期 doi: 10.1016/j.eng.2021.04.014

血清鸟氨酸水平下降与类风湿关节炎缓解情况密切相关——从青藤碱的一项随机双盲临床试验中得到的启示

a Department of Rheumatology, The Southwest Hospital of Army Military Medical University, Chongqing 400038, China
b State Key Laboratory of Dampness Syndrome Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China
c State Key Laboratory of Quality Research in Chinese Medicine & Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology,
Macao 999078, China
d People’s Hospital of Changshou Chongqing, Chongqing 401220, China
e Traditional Chinese Medicine Hospital Dianjiang Chongqing, Chongqing 408300, China
f Medical Management Center, World Federation of Chinese Medicine Societies, Beijing 100101, China

# These authors contributed equally to this work.

收稿日期: 2020-10-14 修回日期: 2021-03-19 录用日期: 2021-04-06 发布日期: 2021-05-18

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摘要

青藤碱(SIN)是中国类风湿关节炎(RA)治疗的常用药物,但目前尚无SIN单药治疗疗效的文献报道。本研究旨在探讨SIN治疗RA的有效性和安全性,并分析鸟氨酸水平与RA患者疾病活动情况的相关性。本项目设计为24周的多中心、随机、安慰剂对照、双盲临床试验,轻中度活动度的RA患者按照1∶1∶1随机分配接受SIN(120 mg,每日两次)、甲氨蝶呤(MTX)(每周10 mg)或SIN + MTX治疗。项目以24周达到ACR50标准的受试者比例,以及根据临床疾病活动指数(CDAI)显示改善的受试者比例为主要疗效指标,并进一步分析24周治疗后的RA受试者疾病活动变化是否与血清鸟氨酸水平相关。在135名受试者中,38名、39名和36名分别接受了SIN、MTX和SIN + MTX的治疗。在SIN治疗组中,52.63%的受试者在治疗24周后达到ACR50标准,与MTX治疗组和SIN + MTX治疗组的结果相当。患者不良反应以肝功能损害和胃肠功能紊乱为主,但SIN组肝功能损害的发生率(1/38)明显低于MTX组(10/39)和SIN + MTX组(8/36)。采用超高效液相-四极杆飞行时间质谱仪(UHPLC-Q-TOF/MS),测定了三个治疗组4个随访时间点共计221份血清样本中的鸟氨酸、瓜氨酸和精氨酸的含量。治疗24周后,血清鸟氨酸水平随着疾病活动度的降低而下降,敏感度为80%,提示鸟氨酸水平可一定程度上预测治疗应答情况。综上所述,SIN对RA患者的疗效与MTX相当,副作用更少,且首次发现血清鸟氨酸水平与类风湿关节炎的缓解密切相关,提示鸟氨酸具有成为类风湿关节炎疗效评价指标的潜在价值。

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