血浆miRNA-320C和miRNA-6088对Ⅱ型糖尿病肾病的诊断价值

doi:10.3969/j.issn.1006-7795.2019.03.026

摘要/Abstract

摘要： 目的研究miRNA-320C （miR-320C）和miRNA-6088（miR-6088）在Ⅱ型糖尿病肾病血浆中的表达，并探讨其对Ⅱ型糖尿病肾病的临床诊断价值。方法选取2015年6月至2016年12月在首都医科大学附属北京安贞医院就诊的56例Ⅱ型糖尿病（type Ⅱ diabetic nephropathy，T2D）患者作为T2D组和105例Ⅱ型糖尿病肾病（diabetic nephropathy，DN）患者作为DN组，另选同时期体检的健康人52例作为正常对照组（normal control，NC）。实时荧光定量PCR检测miR-320C和miR-6088的表达。Pearson法分析miR-320C或miR-6088与其他临床指标之间的相关性，受试者工作特征（receiver operating characteristic，ROC）曲线分析miR-320C和miR-6088对Ⅱ型糖尿病肾病的诊断价值。结果 miR-320C和miR-6088在DN组患者相对表达水平显著高于T2D组（P<0.05）和NC组（P<0.05）。Pearson相关分析显示，miR-C或miR-6088与尿蛋白排泄率（urinary albumin excretion rate，UAER）呈正相关，与肾小球滤过率（estimated glomerular filtration rate，eGFR）呈负相关，而与血浆糖化血红蛋白（human glycated hemoglobin A1C，HbA1C）、三酰甘油（triglyceride，TG）、低密度脂蛋白胆固醇（low density lipoprotein-cholesterol，LDL-C）、糖尿病病程和体质量指数无相关性。ROC曲线分析miR-320C和miR-6088诊断Ⅱ型糖尿病肾病AUC分别为0.834和0.753。结论 miR-320C和miR-6088在Ⅱ型糖尿病肾病患者外周血中高表达，是Ⅱ型糖尿病肾病患者诊断和预后的潜在标志物。

关键词: miR-320C, miR-6088, Ⅱ型糖尿病肾病, 生物标志物

Abstract: Objective To study the diagnosis value of plasma miRNA-320C (miR-320C) and miRNA-6088 (miR-6088) in type Ⅱ diabetic nephropathy (T2D). Methods Fifty-six T2D patients for T2D group, 105 type Ⅱ diabetic nephropathy (DN) for DN group and 52 healthy people for normal control (NC) group were recruited from Jun. 2015 to Dec. 2016 in Beijing Anzhen Hospital, Capital Medicical University. The expression of circulating miR-320C andmiR-6088 were detected by RT-qPCR. Pearson analysis was used to analyze the correlation between miR-320C or miR-6088 and clinical data. And receiver operating characteristic(ROC) curve was drawn to test the diagnostic value of miR-320C and miR-6088.Results The expression of circulating miR-320C and miR-6088 in DN group was higher than NC group (P<0.05) and T2D group (P<0.05). Pearson correlation analysis showed that miR-320C or miR-6088 was positively correlated with urinary albumin excretion rate (UAER), negatively correlated with estimated glomerular filtration rate (eGFR), while had no correlation with the plasma levels of human glycated hemoglobin A1C (HbA1C),triglycerides, low density lipoprotein-cholesterol (LDL-C) and diabetes duration, body mass index. ROC curves of miR-320C and miR-6088 presented an area under curve of 0.834 and 0.753, respectively. After treatment, both miR-320C and miR-6088 expression were significantly decreased (P<0.05).Conclusion Circulating miR-320C and miR-6088 were highly expressed in type Ⅱ diabetic nephropathy, which may serve as useful diagnostic and prognostic biomarkers with type Ⅱ diabetic nephropathy.

Key words: miR-320C, miR-6088, type Ⅱ diabetic nephropathy, biomarker

中图分类号:

R446

王蕤, 吴素萍, 徐品颖. 血浆miRNA-320C和miRNA-6088对Ⅱ型糖尿病肾病的诊断价值[J]. 首都医科大学学报, 2019, 40(3): 466-472.

Wang Rui, Wu Suping, Xu Pinying. Diagnosis value of plasma miRNA-320C and miRNA-6088 in diagnosis of type Ⅱ diabetic nephropathy[J]. Journal of Capital Medical University, 2019, 40(3): 466-472.

参考文献

[1] 中华医学会糖尿病学分会微血管合并症学组.糖尿病肾病防治专家共识(2014年版)[J]. 中华糖尿病杂志,2014,6(11):792-801.
[2] Zhou L, Zou G, Li W, et al. Prevalence of diabetic nephropathy complicating non-diabetic renal disease among Chinese patients with type 2 diabetes mellitus[J]. Eur J Med Res, 2013,18:4-12.
[3] Fried L F, Lewis J. Rebuttal of the pro view:albuminuria is an appropriate therapeutic target in patients with CKD[J]. Clin J Am Soc Nephrol, 2015, 10(6):1095-1098.
[4] Cheng C J, Bahal R, Babar I A, et al. MicroRNA silencing for cancer therapy targeted to the tumor microenvironment[J]. Nature, 2015, 518(7537):107-110.
[5] Yang Y, Xiao L, Li J, et al. Urine miRNAs:potential biomarkers for monitoring progression of early stages of diabetic nephropathy[J]. Med Hypotheses, 2013, 81(2):274-278.
[6] Kato M,Wang M, Chen Z,et al.An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy[J].Nat Commun, 2016, 7:12864-12880.
[7] Bijkerk R, Florijn W, Khairoun M, et al. Acute rejection after kidney transplantation associates with circulating MicroRNas and vascular injury[J].Transplant Direct,2017,3(7):e174.
[8] Deli Ac'X D, Eisele C, Schmid R, et al. Urinary exosomal miRNA signature in type Ⅱ diabetic nephropathy patients[J]. PLoS One, 2016, 11(3):eo150154.
[9] Maclsaac R, Ekinic E I, Premaratne E,et al. The chronic kidney disease-epidemiology collaboration (CKD-EPI) equation does not improve the underestimation of glomerular filtration rate (GFR) in people with diabetes and preserved renal function[J].BMC Nephrol, 2015,16:198.
[10] Piccoli G B, Grassi G, Gabiddu G, et al. Diabetic kidney disease:a syndrome rather than a single disease[J].Rev Diabet Stud, 2015,12(1-2):87-109.
[11] Qian Y, Feldman E, Pennathur S, et al.Mechanisms of glomerulosclerosis in diabetic nephropathy[J]. Diabetes, 2008, 57(6):1439-1445.
[12] Doshi S M, Friedman A N. Diagnosis and management of type 2 diabetic kidney disease[J].Clin J Am Soc Nephrol, 2017,12(8):1366-1373.
[13] 李宛洋, 雷敏,滑丽美.糖尿病肾病患者营养治疗的研究进展[J].临床误诊误治,2017,30(7):110-113.
[14] 滑丽美, 邱建宏,曹婧然.低蛋白饮食对糖尿病肾病治疗效果的评价研究[J].解放军医药杂志,2017,29(8):48-50.
[15] Li J, Zhai X W, Wang H S, et al. Circulating microRNA-21, microRNA-23a, and microRNA-125b as biomarkers for diagnosis and prognosis of burkitt lymphoma in children[J]. Med Sci Monit, 2016, 22:4992-5002.
[16] Yan H J, Ma J Y, Wang L, et al. Expression and significance of circulating microRNA-31 in lung cancer patients[J]. Med Sci Monit, 2015, 21:722-726.
[17] Zhao B, Li H, Liu J, et al. MicroRNA-23b targets Ras GTPase-activating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy[J]. J Am Soc Nephrol, 2016, 27(9):2597-2608.
[18] Putta S, Lanting L, Sun G, et al. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy[J]. J Am Soc Nephrol, 2012, 23(3):458-469.
[19] Chen X, Zhao L, Xing, et al.Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in diabetic nephropathy by relieving the repression of TIMP3 expression[J].Biomed Pharmacother,2018,108:7-14.
[20] Bronisz A, Godlewski J, Wallace J A, et al. Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320[J]. Nat Cell Biol, 2011, 14(2):159-167.
[21] Iwagami Y, Eguchi H, Nagano H, et al. MiR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1[J]. Br J Cancer, 2013, 109(2):502-511.
[22] Song C L, Liu B, Diao H Y, et al.The protective effect of microRNA-320 on left ventricular remodeling after myocardial ischemia-reperfusion injury in the rat model[J]. Int J Mol Sci, 2014, 15(10):17442-17456.
[23] Hamam D, Ali D, Vishnubalaji R, et al. MicroRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells[J]. Cell Death Dis, 2014, 5:e1499.
[24] 朱柄铭, 陈文璟,苏运钦, 等. 血清miR-21在糖尿病肾病中的诊断价值[J].中国病理生理杂志, 2013,29(12):2160-2166.