滋膵饮治疗糖尿病肾病的临床代谢组学研究  

Clinical metabolomics of Zicuiyin in treatment of diabetic kidney disease

作　　者：刘佳[1] 张志丹[2] 吕春晓 杜犀[1] 黄宇虹[1] LIU Jia;ZHANG Zhi-dan;LYU Chun-xiao;DU Xi;HUANG Yu-hong(Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China;Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China)

机构地区：[1]天津中医药大学第二附属医院,天津300250 [2]中国科学院天津工业生物技术研究所,天津300308

出　　处：《中国中药杂志》2024年第2期550-558,共9页China Journal of Chinese Materia Medica

基　　金：国家“重大新药创制”科技重大专项(2015ZX09101043-009);国家自然科学基金青年基金项目(81903768);天津市卫生健康委员会中医中西医结合科研课题(2019070)。

摘　　要：为分析滋膵饮对糖尿病肾病的治疗效果,探究药物可能的作用靶点,收集2019年1—12月在天津中医药大学第二附属医院内分泌科或肾病科就诊的糖尿病肾病患者18例,分为试验组(10例)和对照组(8例),2组患者均在西药常规治疗基础上服用滋膵饮或黄葵胶囊,给药8周。该试验获得天津中医药大学第二附属医院伦理委员会批准(批准号2017-023-01),全部受试者签署知情同意书。结果显示,滋膵饮能有效降低患者的糖化血红蛋白,对疾病发展程度较低(24 h尿蛋白定量<3.5 g)患者的24 h尿蛋白定量、24 h尿微量白蛋白、尿白蛋白肌酐比值、肾小球滤过率均有改善作用。根据尿蛋白水平的差异将全部患者分为2个亚组(24 h尿蛋白定量<3.5 g为A亚组,≥3.5 g为B亚组)。采用UPLC-Q-TOF-MS/MS技术对不同亚组患者基线血清样品进行非靶向代谢组学分析,确定19个潜在生物标志物以区分2个亚组代谢差异,并与临床指标进行相关性分析。其中滋膵饮显效的A亚组中苯丙氨酸、伪尿苷、腺苷3个标志物受其干预显著回调[差异倍数(FC)<0.5,P<0.05]。结果表明,滋膵饮对糖尿病肾病发展程度较低患者的治疗效果更优,作用靶点涉及苯丙氨酸代谢和核苷代谢。This study aimed to analyze the therapeutic effect of Zicuiyin on diabetic kidney disease(DKD) and explore the possible targets of this formula.Eighteen DKD patients treated in the endocrine department or nephrology department of Second Affilia-ted Hospital of Tianjin University of Traditional Chinese Medicine from January to December in 2019 were enrolled and assigned into a test group(n=10) and a control group(n=8).Both groups received routine chemical medicine treatment.In addition,the test group was treated with Zicuiyin and the control group with Huangkui Capsules for 8 weeks.The clinical trial was approved by the Ethics Committee of Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,with the ethical approval No.2017-023-01,and all the patients signed the informed consent form.The results showed that the 8-week treatment with Zicuiyin lowered the level of glycosylated hemoglobin(HbA1c) and recovered the 24 h urinary protein(24hUP),24 h urinary microalbumin(24hmAlb),urine albumin-to-creatinine ratio(UACR),and estimated glomerular filtration rate(eGFR) of the patients with 24hUP<3.5 g.According to the different levels in 24hUP,all the patients were divided into two subgroups(subgroup A with 24hUP<3.5 g and subgroup B with 24hUP≥3.5 g).The ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)-based non-targeted metabolomics analysis was conducted on the baseline serum samples from diffe-rent subgroups of patients.Nineteen biomarker candidates were identified to distinguish the metabolic differences between the two subgroups,and their correlations with clinical indicators were analyzed.Zicuiyin lowered the levels of phenylalanine,pseudouridine,and adenosine [fold change(FC)<0.5,P<0.05] in subgroup A.The results indicated that Zicuiyin was more effective on the DKD patients with low urinary protein levels,and its targets were involved in phenylalanine metabolism and nucleoside metabolism.

关 键 词：糖尿病肾病 滋膵饮 蛋白尿 代谢组学 

分 类 号：R259[医药卫生—中西医结合] R277.5[医药卫生—中医内科学]