血浆基质金属蛋白酶组织抑制剂1、基质金属蛋白酶组织抑制剂2联合检测糖尿病肾脏疾病的临床价值研究  

Clinical exploration of early diagnosis of diabetic kidney disease based on a combined model of plasma cytokines TIMP-1,TIMP-2 and clinical indicators

作　　者：张宁[1] 曹斌 赵冬[1] 柯静 ZHANG Ning;CAO Bin;ZHAO Dong(Department of Center for Endocrinology,Metabolism and Immune Diseases,Beijing Luhe Hospital Affiliated to Capital Medical University,Beijing 101149,China)

机构地区：[1]首都医科大学附属北京潞河医院内分泌代谢与免疫性疾病中心,101149

出　　处：《中国糖尿病杂志》2021年第11期810-815,共6页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81800723)。

摘　　要：目的探讨基质金属蛋白酶组织抑制剂1(TIMP-1)、TIMP-2联合检测DKD的临床价值。方法选取2019年9月至2020年8月于北京潞河医院内分泌科就诊的T2DM患者330例,根据3个月内2次以上UACR结果分为单纯T2DM组(T2DM,n=112)、微量白蛋白尿组(DK1,n=121)及大量白蛋白尿组(DK2,n=97)。采用RayBiotech人细胞因子蛋白芯片筛选,ELISA法验证差异表达细胞因子。Logistic回归分析DKD的影响因素,采用随机森林法进行模型拟合预测。结果蛋白芯片筛选出血浆TIMP-1、TIMP-2、趋化因子16(CXCL16)、血管紧张素1(ANG-1)等4个有统计学差异的因子。与T2DM组比较,DK1、DK2组TIMP-1[(8.37±1.10)vs(6.97±1.16)vs(6.64±1.14)ng/ml,P<0.01]及TIMP-2[(160.97±40.14)vs(118.66±31.11)vs(92.94±35.15)ng/ml,P<0.01]降低。各组ANG-1、CXCL16差异无统计学意义(P>0.05)。Logistic回归分析显示,TIMP-1、TIMP-2、性别、年龄是DKD的影响因素(P<0.05)。TIMP-1、TIMP-2联合性别、年龄对DKD的诊断模型受试者工作特征曲线下面积为0.84,灵敏度85%,特异度81%。结论 DKD患者TIMP-1、TIMP-2随UACR升高而降低。年龄、性别、TIMP-1、TIMP-2联合检测可提高DKD确诊率。Objective To investigate the diagnostic value of tissue inhibitor of matrix metalloproteinase 1(TIMP-1)and TIMP-2 in diabetic kidney disease(DKD).Methods A total of 330 patients with type 2 diabetes mellitus(T2 DM)who were admitted to the Endocrinology Clinic of Beijing Luhe Hospital from September 2019 to August 2020 were enrolled in this study. All the patients were divided into 3 groups according to the results of urinary albumin creatinine ratio(UACR)more than twice in 3 months:non albuminuria group(T2 DM group),microalbuminuria group(DK1 group),and macroalbuminuria group(DK2 group). The factors with significant differences were screened by Ray Biotech human cytokine microarray and verified by ELISA. Then,the diagnostic prediction model of DKD was established by logistic regression analysis and random forest analysis.Results Plasma TIMP-1,TIMP-2,chemokine 16(CXCL16)and angiotensin 1(ANG-1)were screened outby protein microarray. Compared with T2 DM group,TIMP-1 was decreased[(8. 37±1. 10)vs(6. 97±1. 16)vs(6. 64±1. 14)ng/ml,P<0. 01],and TIMP-2 was decreased[(160. 97±40. 14)vs(118. 66±31. 11)vs(92. 94±35. 15)ng/ml,P<0. 01]in DK1 and DK2 groups.ANG-1 and CXCL16 were not different among the three groups(P>0. 05). Logistic regression analysis showed that TIMP-1,TIMP-2 and female were independent protective factors for DKD,while age was an independent risk factor for DKD(P<0. 05). The AUC of TIMP-1 and TIMP-2 combined with sex and age for DKD was 0. 84,the sensitivity was 85%,and the specificity was 81%.Conclusion TIMP-1 and TIMP-2 decreased in DKD patients and showed a downward trend with the increase of urinary UACR. The combined testsof age,sex,TIMP-1 and TIMP-2 may increase the diagnosis rate of DKD.

关 键 词：基质金属蛋白酶组织抑制剂1 基质金属蛋白酶组织抑制剂2 蛋白芯片 糖尿病肾脏疾病 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]