miR-451a在糖尿病肾病肾纤维化中的临床应用研究  

The clinical application of miR-451a in renal fibrosis of patients with diabetic nephropathy

作　　者：钟凌[1] 冯韵霖[2] 杨鸿玲[2] 张萍[2] 李焱鑫[1] 

机构地区：[1]四川省人民医院检验科,四川成都610072 [2]四川省人民医院肾内科,四川成都610072

出　　处：《现代预防医学》2017年第5期941-946,共6页Modern Preventive Medicine

摘　　要：目的研究糖尿病肾病(DN)患者肾组织miR-451a表达量与肾功能、肾纤维化的关系,探讨其临床应用价值。方法对DN患者进行肾活检,活检组织进行病理分级的同时提取RNA通过q PCR分析miR-451a、p15INK4b(p15)、E-caherin、α-SMA的表达变化;提取总蛋白分析各指标蛋白水平变化;并分析尿素、肌酐、尿酸、尿微量白蛋白/肌酐比(ACR)的改变。结果共收集DN患者46例,年龄39~64岁,男28例,女18例。病理分级为I级2例,Ⅱa级6例,Ⅱb级8例,Ⅲ级26例,IV级4例。DN组肾组织miR-451a表达量为对照组的0.2倍(P<0.05),p15的mRNA表达量为5.3倍(P<0.05)。随纤维化加重,miR-451a、E-caherin水平逐步下降,p15、α-SMA逐步升高(趋势分别为42.21、35.36、31.43、45.96,P<0.001)。miR-451a水平与p15、α-SMA、尿素、ACR呈负相关(r=-0.88,-0.83,-0.87,-0.86,P<0.05),与E-cadherin呈正相关(r=0.86,P<0.05)。P15的蛋白表达量(I级为对照组的2.62倍,Ⅱa级3.00倍,Ⅱb级3.76倍,Ⅲ级3.88倍,IV级4.58倍)、α-SMA的蛋白水平(升至2.24倍,2.82倍,3.00倍,3.10倍,3.64倍),而E-cadherin依次降至0.96,0.61,0.53,0.45,0.29。结论 DN肾纤维化过程中肾miR-451a呈低表达,与周期阻滞、EMT、肾功能存在相关性,可能成为纤维化新的评价指标及治疗靶标。Objective To study the expression level of miR -451a in kidney tissue of DN patients and analysis the correlation with kidney function and renal fibrosis, to explore the clinical value of the application. Methods Renal biopsy was performed on DN patients,then the tissue was pathologically classified and the DNA was extracted at the same time. The expressional variety of miR -451a,p15INK4b（p15 ,E - eaherin and α - SMA was analysed by qPCR. The variety of each kind of indicator protein and the change of urea, creatinine, uric acid, urinary albumin/creafinine ratio （ACR） were analysed with the way of extracting the total protein. Results 46 hospitalized patients in nephrology department were included,whose age ranged from 39 to 64 years old,28 males and 18 females. Pathological classification was as follows ：2 cases were grade 1,6 cases were grade Ⅱ a,8 cases were grade Ⅱb,26 cases were grade Ⅲ and 4 cases were grade IV. The expression level of miR - 451 a in the case group was only 20% of the control group（P 〈 0.05 ）, while the expression level of pl5INK4b was 5.3 times（ P 〈 0.05 ）more than the control group. With the worse of fibrosis,the expression level of miR- 451a and E -eaherin were gradually declined, while pl5 and ct - SMA showed a gradually increasing trend （ e2 = 42.21,35.36,31.43,45.96, P 〈 0. 001 ）. In the process of renal fibrosis, the expression level of miR -451a was negatively related to the expression level of p15, α -SMA, urea and ACR （r = -0.88, - 0. 83, - 0. 87, - 0. 86,P 〈 0.05） and passively corrected with E - cadherin （ r = 0. 86, P 〈 0.05）. The expressional protein level of P15 in the case group were 2.62,3.00,3.76 and 3.88 times more than in the control group in grade I, grade Ⅱa, grade Ⅱb, grade Ⅲ and grade IV respectively. While the expressional protein level of E - cadherin reduced at 0.61,0.53,0.45 and 0.29 times respectively. Conclusion In renal tissue, miR -451a shows low expression level in the process of fibrosis. It is related w

关 键 词：miR-451a 细胞周期阻滞 纤维化 糖尿病肾病 

分 类 号：R113[医药卫生—公共卫生与预防医学]