miR-126、Transferrin、miR-133b、miR-342和Cystatin C对2型糖尿病肾病的诊断价值
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摘要
目的探讨miR-126、Transferrin、miR-133b、miR-342和Cystatin C对2型糖尿病肾病的诊断价值。方法选取2型糖尿病肾病患者30例为糖尿病肾病组,2型糖尿病非肾病患者30例为糖尿病非肾病组,同时选取健康体检者30例为对照组,检测3组受试者血清中miR-126和Transferrin的水平,尿中miR-133b、miR-342和Cystatin C的水平。用ROC曲线下面积分析miR-126、Transferrin、miR-133b、miR-342和Cystatin C对2型糖尿病肾病的诊断价值。结果糖尿病肾病患者的miR-126的相对表达量明显低于糖尿病非肾病患者和健康体检者(P<0.05),而其miR-133b和miR-342的相对表达量、Cystatin C和Transferrin的表达量明显高于糖尿病非肾病患者和健康体检者(P <0. 05)。糖尿病非肾病患者miR-126的相对表达量明显低于健康体检者(P <0.05),而其miR-133b的相对表达量和Cystatin C和Transferrin的表达量明显高于健康体检者(P<0.05)。2型糖尿病肾病患者与非2型糖尿病肾病人员的miR-126、miR-133b、miR-342、Cystatin C和Transferrin的灵敏度分别为96%、83%、70%、77%、83%;特异性分别为41%、75%、82%、88%、80%。四项联合检测的灵敏度为97%、特异性为77%,准确率为83%。结论 miR-126、Transferrin、miR-133b、miR-342和Cystatin C可作为诊断2型糖尿病肾病的潜在标志物。
Objective To investigate the diagnostic values of miR-126,Transferrin,miR-133 b, miR-342 and cystatin C in type 2 diabetic nephropathy. Methods 30 patients with type 2 diabetic nephropathy were selected as the diabetic nephropathy group, while 30 patients with type 2 diabetes non-nephropathy were selected as the diabetic non-nephropathy group,and 30 healthy subjects were also selected as the control group. Three groups of serum miR-126 were then detected,as well as the contents of Transferrin,miR-133 b,miR-342 and Cystatin C in urine. The area under the ROC curve was used to estimate the diagnostic value of miR-126,Transferrin, miR-133 b, miR-342 and cystatin C for type 2 diabetic nephropathy. Results The relative expression of miR-126 in diabetic nephropathy patients was significantly lower than that in diabetic nonnephrotic patients and healthy subjects(P <0.05), while the relative expression levels of miR-133 b and miR-342 were correlated with cysstatin C and Transferrin. The expression level was significantly higher than that of patients with diabetes non-nephropathy and healthy subjects(P <0. 05). The relative expression of miR-126 in diabetic non-nephropathy patients was significantly lower than that in healthy subjects(P <0. 05), while the relative expressions of miR-133 b, cystatin C and Transferrin were significantly higher than those in healthy subjects(P <0.05). The sensitivities of miR-126,miR-133 b,miR-342,cystatin C and Transferrin in patients with type 2 diabetic nephropathy and non-type 2 diabetic nephropathy were 96%,83%,70%,77%,and 83%, respectively; while the specificities were 41%, 75%, 82%, 88%, and 80%, respectively. The sensitivity of the four markers joint tests was 97%,while the specificity was 77%,and the accuracy was83%. Conclusion miR-126,Transferrin,miR-133 b,miR-342 and cystatin C can be used as potential markers for the diagnosis of type 2 diabetic nephropathy.
Objective To investigate the diagnostic values of miR-126,Transferrin,miR-133 b, miR-342 and cystatin C in type 2 diabetic nephropathy. Methods 30 patients with type 2 diabetic nephropathy were selected as the diabetic nephropathy group, while 30 patients with type 2 diabetes non-nephropathy were selected as the diabetic non-nephropathy group,and 30 healthy subjects were also selected as the control group. Three groups of serum miR-126 were then detected,as well as the contents of Transferrin,miR-133 b,miR-342 and Cystatin C in urine. The area under the ROC curve was used to estimate the diagnostic value of miR-126,Transferrin, miR-133 b, miR-342 and cystatin C for type 2 diabetic nephropathy. Results The relative expression of miR-126 in diabetic nephropathy patients was significantly lower than that in diabetic nonnephrotic patients and healthy subjects(P <0.05), while the relative expression levels of miR-133 b and miR-342 were correlated with cysstatin C and Transferrin. The expression level was significantly higher than that of patients with diabetes non-nephropathy and healthy subjects(P <0. 05). The relative expression of miR-126 in diabetic non-nephropathy patients was significantly lower than that in healthy subjects(P <0. 05), while the relative expressions of miR-133 b, cystatin C and Transferrin were significantly higher than those in healthy subjects(P <0.05). The sensitivities of miR-126,miR-133 b,miR-342,cystatin C and Transferrin in patients with type 2 diabetic nephropathy and non-type 2 diabetic nephropathy were 96%,83%,70%,77%,and 83%, respectively; while the specificities were 41%, 75%, 82%, 88%, and 80%, respectively. The sensitivity of the four markers joint tests was 97%,while the specificity was 77%,and the accuracy was83%. Conclusion miR-126,Transferrin,miR-133 b,miR-342 and cystatin C can be used as potential markers for the diagnosis of type 2 diabetic nephropathy.
引文
[1]陈灿锋,王家健,侯晓涛,等.2型糖尿病肾病病理分型特点与尿蛋白的关系[J].标记免疫分析与临床,2017,24(2):183-188.
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[3]卢佩颖,谷卫,陈岳明.2型糖尿病患者血清miR. 126表达的临床意义[J].心脑血管病防治,2012,12(1):10-11.
[4]韩辉,林书典,陈道军,等.血清微小核糖核酸-133b水平与老年糖尿病肾病患者肾脏损伤及预后的相关性[J].中华老年多器官疾病杂志,2018,17(6):420-424.
[5]孙晓兰,陈敏.2型糖尿病不同尿白蛋白排泄率患者血清中miR-342-5p、miR-423-5p的表达量及临床意义[J].海南医学院学报,2017,23(1):62-65.
[6]辛佳音,魏枫,苏日娜,等.血、尿CystatinC对2型糖尿病肾病的临床意义[C].中华医学会第八次全国内分泌学学术会议.2009.
[7]李竞,包艳,甘佩珍.糖尿病肾病患者血及尿转铁蛋白测定的临床意义[J].临床内科杂志,2002,19(6):454-455.
[8] MOGENSEN C E, CHRISTENSEN C K, VITTINGHUS E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy[J]. Diabetes, 1983,32(Suppl 2):64-78.
[9]李雪莉,姜亚云,张景玲,等.WHO与美国糖尿病学会糖尿病诊断标准异同的探讨[J].中华内分泌代谢杂志,2000,16(2):87-90.
[10]杨霓芝,刘旭生.糖尿病肾病诊断、辨证分型及疗效评定标准(试行方案)[J].上海中医药杂志,2007,41(7):7-8.
[11]李梅爱,周珍文,李建明,等.血清半胱氨酸蛋白酶抑制剂C和同型半胱氨酸联合检测在儿童早期糖尿病肾病中的诊断意义[J].热带医学杂志,2012,12(1):47-49.
[12]黄山,洪燕英,张雅然.肾组织补体Clq沉积水平在糖尿病肾病的临床应用价值研究[J].标记免疫分析与临床,2017,24(9):979-981.
[13]韩海燕,路建饶,刘文瑞,等.叶氏糖肾方对临床期糖尿病肾病炎症因子及血液动力学的影响[J].中国中西医结合肾病杂志,2018,19(1):20-24.
[14]陈娅,丁涵露,李贵森,等.Ad-FLT-1/PC对糖尿病肾病动脉粥样硬化大鼠细胞凋亡及氧化应激的影响[J].中华肾脏病杂志,2017,33(10):770-774.
[15]唐慧,伍海姗,杨怡,等.外泌体源性microRNA在疾病诊疗中的研究进展[J].中南大学学报(医学版),2015,40(11):1270-1275.
[16]罗艳,胡桂英,李长勇.糖尿病患者miRNA-29水平与胰岛素抵抗的相关性[J].中国老年学杂志,2018,38(5):1036-1039.
[17]吴雪纯,贾永平.miR-126在心血管疾病中的研究进展[J].中华临床医师杂志(电子版),2016,10(12):1800-1803.
[18]郭晓莉,陈艳,马卫国,等.血液循环中miR-126作为标志物对2型糖尿病肾脏疾病患者诊断的临床意义[J].临床肾脏病杂志,2017,17(6):361-365.
[19]郝学增,郑相颖,王红艳,等.通脉养心丸对冠心病合并糖尿病PCI术后患者心肌核素显影SSS评分与血浆标志miRNA-126影响的研究[J].临床和实验医学杂志,2018,17(1):1-4.
[20]方淑君,王成,王静,等.2型糖尿病微血管并发症患者血清miR-16,miR-126和miR-221水平检测及临床意义[J].现代检验医学杂志,2016,31(5):9-13.
[21] WANG H, PENG W, SHEN X, et al. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease[J]. Braz J Med Biol Res,2012,45(12):1308-1314.
[22] MATBOLI M,EISSA S,IBRAHIM D,et al. Caffeic acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin-induced diabetic rat[J]. Sci Rep, 2017, 7(1):2263.
[23] GUO Y,TANG CY,MAN X F,et al. Insulin receptor substrate-1time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342[J]. FASEB J, 2016, 30(12):4214-4226.
[24] ZOU C, XIE R, BAO Y, et al. Iron chelator alleviates tubulointerstitial fibrosis in diabetic nephropathy rats by inhibiting the expression of tenascinC and other correlation factors[J].Endocrine,2013,44(3):666-674.
[25]彭健,张耀婷,陈杰,等.转铁蛋白的结构功能和潜在临床应用价值[J].中国现代医学杂志,2017,27(26):56-60.
[26]沈清,甘华,谯林,等.血清Cystatin C对肾小球滤过功能价值的探讨[J].重庆医学,2002,31(6):458-460.
[27]曹华军,王旭,范存琳,等.尿Cystatin C与肾小管功能的关系[C].中日检验医学论坛暨检验与临床学术会议.2004.
[28]贾汝汉,高苹.糖尿病肾病肾小管间质病变研究进展[J].中国中西医结合肾病杂志,2005,6(6):311-314.
[2]吕金勇,谭向龙,刘荣.血清microRNA作为胰腺癌早期诊断肿瘤标志物的研究进展[J].世界最新医学信息文摘,2016,16(88):15-16.
[3]卢佩颖,谷卫,陈岳明.2型糖尿病患者血清miR. 126表达的临床意义[J].心脑血管病防治,2012,12(1):10-11.
[4]韩辉,林书典,陈道军,等.血清微小核糖核酸-133b水平与老年糖尿病肾病患者肾脏损伤及预后的相关性[J].中华老年多器官疾病杂志,2018,17(6):420-424.
[5]孙晓兰,陈敏.2型糖尿病不同尿白蛋白排泄率患者血清中miR-342-5p、miR-423-5p的表达量及临床意义[J].海南医学院学报,2017,23(1):62-65.
[6]辛佳音,魏枫,苏日娜,等.血、尿CystatinC对2型糖尿病肾病的临床意义[C].中华医学会第八次全国内分泌学学术会议.2009.
[7]李竞,包艳,甘佩珍.糖尿病肾病患者血及尿转铁蛋白测定的临床意义[J].临床内科杂志,2002,19(6):454-455.
[8] MOGENSEN C E, CHRISTENSEN C K, VITTINGHUS E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy[J]. Diabetes, 1983,32(Suppl 2):64-78.
[9]李雪莉,姜亚云,张景玲,等.WHO与美国糖尿病学会糖尿病诊断标准异同的探讨[J].中华内分泌代谢杂志,2000,16(2):87-90.
[10]杨霓芝,刘旭生.糖尿病肾病诊断、辨证分型及疗效评定标准(试行方案)[J].上海中医药杂志,2007,41(7):7-8.
[11]李梅爱,周珍文,李建明,等.血清半胱氨酸蛋白酶抑制剂C和同型半胱氨酸联合检测在儿童早期糖尿病肾病中的诊断意义[J].热带医学杂志,2012,12(1):47-49.
[12]黄山,洪燕英,张雅然.肾组织补体Clq沉积水平在糖尿病肾病的临床应用价值研究[J].标记免疫分析与临床,2017,24(9):979-981.
[13]韩海燕,路建饶,刘文瑞,等.叶氏糖肾方对临床期糖尿病肾病炎症因子及血液动力学的影响[J].中国中西医结合肾病杂志,2018,19(1):20-24.
[14]陈娅,丁涵露,李贵森,等.Ad-FLT-1/PC对糖尿病肾病动脉粥样硬化大鼠细胞凋亡及氧化应激的影响[J].中华肾脏病杂志,2017,33(10):770-774.
[15]唐慧,伍海姗,杨怡,等.外泌体源性microRNA在疾病诊疗中的研究进展[J].中南大学学报(医学版),2015,40(11):1270-1275.
[16]罗艳,胡桂英,李长勇.糖尿病患者miRNA-29水平与胰岛素抵抗的相关性[J].中国老年学杂志,2018,38(5):1036-1039.
[17]吴雪纯,贾永平.miR-126在心血管疾病中的研究进展[J].中华临床医师杂志(电子版),2016,10(12):1800-1803.
[18]郭晓莉,陈艳,马卫国,等.血液循环中miR-126作为标志物对2型糖尿病肾脏疾病患者诊断的临床意义[J].临床肾脏病杂志,2017,17(6):361-365.
[19]郝学增,郑相颖,王红艳,等.通脉养心丸对冠心病合并糖尿病PCI术后患者心肌核素显影SSS评分与血浆标志miRNA-126影响的研究[J].临床和实验医学杂志,2018,17(1):1-4.
[20]方淑君,王成,王静,等.2型糖尿病微血管并发症患者血清miR-16,miR-126和miR-221水平检测及临床意义[J].现代检验医学杂志,2016,31(5):9-13.
[21] WANG H, PENG W, SHEN X, et al. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease[J]. Braz J Med Biol Res,2012,45(12):1308-1314.
[22] MATBOLI M,EISSA S,IBRAHIM D,et al. Caffeic acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin-induced diabetic rat[J]. Sci Rep, 2017, 7(1):2263.
[23] GUO Y,TANG CY,MAN X F,et al. Insulin receptor substrate-1time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342[J]. FASEB J, 2016, 30(12):4214-4226.
[24] ZOU C, XIE R, BAO Y, et al. Iron chelator alleviates tubulointerstitial fibrosis in diabetic nephropathy rats by inhibiting the expression of tenascinC and other correlation factors[J].Endocrine,2013,44(3):666-674.
[25]彭健,张耀婷,陈杰,等.转铁蛋白的结构功能和潜在临床应用价值[J].中国现代医学杂志,2017,27(26):56-60.
[26]沈清,甘华,谯林,等.血清Cystatin C对肾小球滤过功能价值的探讨[J].重庆医学,2002,31(6):458-460.
[27]曹华军,王旭,范存琳,等.尿Cystatin C与肾小管功能的关系[C].中日检验医学论坛暨检验与临床学术会议.2004.
[28]贾汝汉,高苹.糖尿病肾病肾小管间质病变研究进展[J].中国中西医结合肾病杂志,2005,6(6):311-314.