糖尿病视网膜病变患者血清miRNA的临床价值
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摘要
目的探讨糖尿病视网膜病变(diabetic retinopathy,DR)患者血清miRNA的临床价值。方法选取2017年1月至12月在本院内分泌科住院治疗的单纯2型糖尿病(diabetes mellitus,DM)患者及同期眼科住院治疗的DR患者各60例,比较两组患者空腹血清生化指标,实时荧光定量PCR检测两组患者血清中miRNA-451、miRNA-221、miRNA-200b的表达水平,Pearson相关分析法分析DR患者血清中3种miRNA与各生化指标的相关性,多因素Logistic回归分析DR发生的危险因素,ROC曲线分析单个miRNA及三者联合对DR风险预测的指导价值。结果 DM组患者血清中空腹血糖(fasting plasma glucose,FPG)、尿白蛋白/肌酐(urinary albumin/creatinine,UACR)、糖化血红蛋白(hemoglobin A1c,HbAlc)均明显低于DR组,差异均有统计学意义(均为P<0.05);DM组中miRNA-451、miRNA-221及miRNA-200b水平均明显低于DR组,差异均有统计学意义(均为P<0.05);DR组患者血清中3种miRNA分别与UACR、HbAlc及FPG呈正相关关系(均为P<0.05),且三者之间相互呈正相关关系(均为P<0.05)。多因素Logistic回归分析显示,UACR、HbAlc、FPG、miRNA-451、miRNA-221及miRNA-200b是DR发生的独立危险因素;miRNA-451、miRNA-221及miRNA-200b的ROC曲线下面积分别为0.722、0.823及0.761,具有较高的诊断价值,三者联合曲线下面积为0.938,优于单项miRNA检测结果,诊断价值最高。结论 DR患者存在着血清miRNA-451、miRNA-221及miRNA-200b异常高表达,并可能参与了DR的发生发展过程,可作为DM向DR发展风险的血清生物学指标。
Objective To investigate the clinical value of serum miRNA in patients with diabetic retinopathy(DR).Methods Totally 60 diabetes mellitus(DM) patients(DM group) hospitalized in the Endocrinology Department of our hospital and 60 DR patients(DR group) hospitalized in ophthalmology department at the same time from January to December 2017 were selected.The fasting serum biochemical indexes of the two groups were compared.Real-time fluorescence quantitative PCR was used to detect the expression levels of miRNA-451,miRNA-221 and miRNA-200 b in serum of two groups.Pearson correlation analysis was used to analyze the correlation between the three miRNA and biochemical indicators in serum of DR patients.Multivariate logistic regression was used to analyze the risk factors of DR.ROC curve was used to analyze the guiding value of single miRNA and their combination in DR risk prediction.Results DM patients serum biochemical index in fasting plasma glucose(FPG),urinary albumin/creatinine(UACR),glycosylated hemoglobin(HbAlc) was lower than that in group DR,differences were statistically significant(all P<0.05).The levels of miRNA-451,miRNA-221 and miRNA-200 b in the DM group were significantly lower than those in the DR group,with statistically significant differences(all P<0.05).Three miRNA in the serum of patients in the DR group were positively correlated with UACR,HbAlc and FPG,respectively(all P<0.05),and the three miRNA were positively correlated with each other(all P<0.05).Multivariate Logistic regression analysis showed that UACR,HbAlc,FPG,miRNA-451,miRNA-221 and miRNA-200 b were independent risk factors for the occurrence of DR.The area under the ROC curve analysis of miRNA-451,miRNA-221 and miRNA-200 b was 0.722,0.823 and 0.761,respectively,suggesting high diagnostic value.The area under the combined curve of the three was 0.938,which was better than the detection results of single miRNA and had the highest diagnostic value.Conclusion Abnormal high expression of miRNA-451,miRNA-221 and miRNA-200 b in serum of DR patients may be involved in the occurrence and development of DR,which can be used as a serum biological indicator of the risk for DM to develop to DR.
Objective To investigate the clinical value of serum miRNA in patients with diabetic retinopathy(DR).Methods Totally 60 diabetes mellitus(DM) patients(DM group) hospitalized in the Endocrinology Department of our hospital and 60 DR patients(DR group) hospitalized in ophthalmology department at the same time from January to December 2017 were selected.The fasting serum biochemical indexes of the two groups were compared.Real-time fluorescence quantitative PCR was used to detect the expression levels of miRNA-451,miRNA-221 and miRNA-200 b in serum of two groups.Pearson correlation analysis was used to analyze the correlation between the three miRNA and biochemical indicators in serum of DR patients.Multivariate logistic regression was used to analyze the risk factors of DR.ROC curve was used to analyze the guiding value of single miRNA and their combination in DR risk prediction.Results DM patients serum biochemical index in fasting plasma glucose(FPG),urinary albumin/creatinine(UACR),glycosylated hemoglobin(HbAlc) was lower than that in group DR,differences were statistically significant(all P<0.05).The levels of miRNA-451,miRNA-221 and miRNA-200 b in the DM group were significantly lower than those in the DR group,with statistically significant differences(all P<0.05).Three miRNA in the serum of patients in the DR group were positively correlated with UACR,HbAlc and FPG,respectively(all P<0.05),and the three miRNA were positively correlated with each other(all P<0.05).Multivariate Logistic regression analysis showed that UACR,HbAlc,FPG,miRNA-451,miRNA-221 and miRNA-200 b were independent risk factors for the occurrence of DR.The area under the ROC curve analysis of miRNA-451,miRNA-221 and miRNA-200 b was 0.722,0.823 and 0.761,respectively,suggesting high diagnostic value.The area under the combined curve of the three was 0.938,which was better than the detection results of single miRNA and had the highest diagnostic value.Conclusion Abnormal high expression of miRNA-451,miRNA-221 and miRNA-200 b in serum of DR patients may be involved in the occurrence and development of DR,which can be used as a serum biological indicator of the risk for DM to develop to DR.
引文
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[8] ZHANG X L,GAO Y F.Expression and significance of mir-195 in vitreous and proliferative membrane tissues of eyes with proliferative diabetic retinopathy[J].Shandong Med J,2017,57(16):74-76.张小露,高永峰.增生型糖尿病视网膜病变患眼玻璃体、增生膜组织miR-195表达及意义[J].山东医药,2017,57(16):74-76.
[9] LIN X,WANG J,YUN L,JIANG S,LI L,CHEN X,et al.Association between LEKR1-CCNL1,IGSF21-KLHDC7A gene polymorphism and diabetic retinopathy of type 2 diabetes mellitus in Chinese Han population[J].J Gene Med,2016,18(10):282-287.
[10] JONSSON K B,FRYDKJAER-OLSEN U,GRAUSLUND J.Vascular changes and neurodegeneration in the early stages of diabetic retinopathy:which comes first[J].Ophthalmic Res,2016,56(1):1-9.
[11] LIU G Q,YANG T T.Research progress on the relationship between microrna-21/signal transduction and transcriptional activator 3 signaling pathway regulation and tumor[J].J Xinxiang Med Univ,2016,33(4):332-335.刘国庆,杨廷桐.微小RNA-21/信号传导及转录激活因子3信号通路调控与肿瘤的关系研究进展[J].新乡医学院学报,2016,33(4):332-335.
[12] GOMAA A R,ELSAYED E T,MOFTAH R F.MicroRNA-200b expression in the vitreous humor of patients with proliferative diabetic retinopathy[J].Ophthalmic Res,2017,58(3):168-175.
[13] BARCELONA P F,SITARAS N,GALAN A,ESQUIVA G,JMAEFF S,JIAN Y,et al.p75NTR and its ligand ProNGF activate paracrine mechanisms etiological to the vascular,inflammatory,and neurodegenerative pathologies of diabetic retinopathy[J].J Neurosci,2016,36(34):8826-8841.
[14] SU L,WANG L H,CHE H,LIANG M H,FU X L.Research progress on microRNA regulation of diabetes and its complications[J].J Clin Exp Med,2017,16(23):2391-2393.苏琳,王丽宏,车慧,梁梅花,付雪莲.microRNA调控糖尿病及其并发症发生发展的研究进展[J].临床和实验医学杂志,2017,16(23):2391-2393.
[15] LU Q,ZHANG J,ZHAO N,WANG H,TONG Q,WANG S.Association of IL-6 gene (-174 and-572 G/C) polymorphisms with proliferative diabetic retinopathy of type 2 diabetes in a Chinese population[J].Ophthalmic Res,2017,58(3):162-167.
[16] ZHANG Y,JIANG X,BO J,YIN L,CHEN H,WANG Y,et al.Risk of stroke and coronary heart disease among various levels of blood pressure in diabetic and nondiabetic Chinese patients[J].J Hypertens,2018,36(1):93-100.
[17] JINDAL V.Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy[J].Mol Neurobiol,2015,51(3):878-884.
[18] ALTMANN C,SCHMIDT M.The role of microglia in diabetic retinopathy:inflammation,microvasculature defects and neurodegeneration[J].Int J Mol Sci,2018,19(1):110.
[19] FU C Y.Expression of miR-93 and miR-21 in patients with diabetic retinopathy and its clinical value[J].Rec Adv Ophthalmol,2017,37(12):1161-1164.符春艳.miR-93及miR-21在糖尿病视网膜病变患者中的表达及其临床价值[J].眼科新进展,2017,37(12):1161-1164.
[20] LI E H,HUANG Q Z,LI G C,XIANG Z Y,ZHANG X.Effects of microRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene[J].Biosci Rep,2017,37(2):1-14.
[2] JOGLEKAR M V,JANUSZEWSKI A S,JENKINS A J,HARDIKAR A A.Circulating microRNA biomarkers of diabetic retinopathy[J].Diabetes,2016,65(1):22-24.
[3] NIE C,ZHANG L,ZHANG J W,WANG Y,LUO X Q.Differences in gene expression profiles of retinal microvascular endothelial cells induced by cobalt chloride in hypoxic human embryos[J].Chin J Appl Clin Pediatr,2017,32(2):112.聂川,张亮,张嘉雯,王越,罗先琼.氯化钴诱导缺氧人胚视网膜微血管内皮细胞基因表达谱差异研究[J].中华实用儿科临床杂志,2017,32(2):112.
[4] CHEN Q,QIU F,ZHOU K,MATLOCK H G,TAKAHASHI Y,RAIALA R V S,et al.Pathogenic role of microRNA-21 in diabetic retinopathy through down-regulation of PPARα[J].Diabetes,2017,66(6):1671-1682.
[5] ZENG K H,WANG Y,DENG B,YU X M,SONG Y,ZHOU X,et al.Regulation of resveratrol expression of microrna-29b inhibits hyperglycemia induced retinal müller cell apoptosis in rats[J].J Appl Chin Med,2017,14(4):22-26.曾凯宏,王元,邓波,余雪梅,宋怡,周雪,等.白藜芦醇调节微小RNA-29b表达抑制高糖诱导的大鼠视网膜müller细胞凋亡[J].实用医院临床杂志,2017,14(4):22-26.
[6] YE E A,STEINLE J J.Regulatory role of microRNA on inflammatory responses of diabetic retinopathy[J].NRR,2017,12(4):580.
[7] ESTEVEZ J,KAIDONIS G,HENDERSON T.Association of disease-specific causes of visual impairment and 10-year mortality amongst Indigenous Australians:the Central Australian Ocular Health Study[J].Clin Exp Ophthalmol,2018,46(1):18-24.
[8] ZHANG X L,GAO Y F.Expression and significance of mir-195 in vitreous and proliferative membrane tissues of eyes with proliferative diabetic retinopathy[J].Shandong Med J,2017,57(16):74-76.张小露,高永峰.增生型糖尿病视网膜病变患眼玻璃体、增生膜组织miR-195表达及意义[J].山东医药,2017,57(16):74-76.
[9] LIN X,WANG J,YUN L,JIANG S,LI L,CHEN X,et al.Association between LEKR1-CCNL1,IGSF21-KLHDC7A gene polymorphism and diabetic retinopathy of type 2 diabetes mellitus in Chinese Han population[J].J Gene Med,2016,18(10):282-287.
[10] JONSSON K B,FRYDKJAER-OLSEN U,GRAUSLUND J.Vascular changes and neurodegeneration in the early stages of diabetic retinopathy:which comes first[J].Ophthalmic Res,2016,56(1):1-9.
[11] LIU G Q,YANG T T.Research progress on the relationship between microrna-21/signal transduction and transcriptional activator 3 signaling pathway regulation and tumor[J].J Xinxiang Med Univ,2016,33(4):332-335.刘国庆,杨廷桐.微小RNA-21/信号传导及转录激活因子3信号通路调控与肿瘤的关系研究进展[J].新乡医学院学报,2016,33(4):332-335.
[12] GOMAA A R,ELSAYED E T,MOFTAH R F.MicroRNA-200b expression in the vitreous humor of patients with proliferative diabetic retinopathy[J].Ophthalmic Res,2017,58(3):168-175.
[13] BARCELONA P F,SITARAS N,GALAN A,ESQUIVA G,JMAEFF S,JIAN Y,et al.p75NTR and its ligand ProNGF activate paracrine mechanisms etiological to the vascular,inflammatory,and neurodegenerative pathologies of diabetic retinopathy[J].J Neurosci,2016,36(34):8826-8841.
[14] SU L,WANG L H,CHE H,LIANG M H,FU X L.Research progress on microRNA regulation of diabetes and its complications[J].J Clin Exp Med,2017,16(23):2391-2393.苏琳,王丽宏,车慧,梁梅花,付雪莲.microRNA调控糖尿病及其并发症发生发展的研究进展[J].临床和实验医学杂志,2017,16(23):2391-2393.
[15] LU Q,ZHANG J,ZHAO N,WANG H,TONG Q,WANG S.Association of IL-6 gene (-174 and-572 G/C) polymorphisms with proliferative diabetic retinopathy of type 2 diabetes in a Chinese population[J].Ophthalmic Res,2017,58(3):162-167.
[16] ZHANG Y,JIANG X,BO J,YIN L,CHEN H,WANG Y,et al.Risk of stroke and coronary heart disease among various levels of blood pressure in diabetic and nondiabetic Chinese patients[J].J Hypertens,2018,36(1):93-100.
[17] JINDAL V.Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy[J].Mol Neurobiol,2015,51(3):878-884.
[18] ALTMANN C,SCHMIDT M.The role of microglia in diabetic retinopathy:inflammation,microvasculature defects and neurodegeneration[J].Int J Mol Sci,2018,19(1):110.
[19] FU C Y.Expression of miR-93 and miR-21 in patients with diabetic retinopathy and its clinical value[J].Rec Adv Ophthalmol,2017,37(12):1161-1164.符春艳.miR-93及miR-21在糖尿病视网膜病变患者中的表达及其临床价值[J].眼科新进展,2017,37(12):1161-1164.
[20] LI E H,HUANG Q Z,LI G C,XIANG Z Y,ZHANG X.Effects of microRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene[J].Biosci Rep,2017,37(2):1-14.
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