血清miR-141水平与糖尿病肾病患者肾脏损伤及远期预后的关系

Relationship between serum miR-141 levels and renal injury and long-term prognosis in diabetic nephropathy patients

目的探讨血清miR-141水平与糖尿病肾病(DN)患者肾脏损伤及远期预后的关系。方法收集2012年1月至2015年12月的114例DN患者及119例健康体检者(对照组)的血清标本并采用实时定量PCR检测miR-141水平,分析血清miR-141水平与常见临床指标(性别、年龄、BMI、糖尿病病程、蛋白尿定量、血钙、空腹血糖、Hb A1c及e GFR)的关系,采用肾小球分级、间质性纤维化和小管萎缩评分(IFTA)及间质炎症来评价肾脏损伤情况,并分析不同肾脏损伤程度的miR-141水平,根据miR-141水平的中位值分组后分析miR-141水平与预后的关系。结果 q PCR检测发现DN患者的血清miR-141水平为(6.312±1.804)(中位值为5.816),高于健康对照组的(1.247±0.219),差异有统计学意义(P<0.05)。DN患者的血清miR-141水平与性别、年龄和血钙无关,但与BMI、糖尿病病程、蛋白尿定量、空腹血糖、Hb A1c及e GFR有关(P<0.05);DN患者的血清miR-141水平与肾小球分级、IFTA及间质炎症均有关,且随着肾脏病理损伤程度的增加,血清miR-141水平和高表达率均升高(P<0.05)。经Spearman相关分析发现,DN患者的血清miR-141水平与肾小球分级、IFTA和间质炎症均呈正相关,相关系数依次为0.329、0.226和0.426(P<0.05)。114例DN患者有42例在随访期间进入终末期肾病(ESRD),其血清miR-141水平为(7.153±2.018),高于72例未进入ESRD的(5.821±1.775),差异均有统计学意义(P<0.05),且miR-141高水平组相对于低水平进入ESRD的风险升高6.333倍。结论 DN患者的血清miR-141水平升高,且其水平与DN患者肾脏损伤及预后有关,miR-141较高者的肾脏损伤程度较严重且预后较差,在DN病情预测及预后评估上有一定价值。

Objective To investigate the relationship between serum miR-141 level and renal injury and long-term prognosis in diabetic nephropathy（ DN） patients. Methods From January 2012 to December 2015,114 serum samples of DN patients and 119 healthy subjects（ control） were collected and detected by real-time quantitative PCR. The relationship between serum miR-141 level and common clinical indicators（ gender,age,BMI,duration of diabetes,urine protein quantity,blood calcium,fasting blood glucose,Hb A1 c and e GFR） were analyzed.The glomerular grading,interstitial fibrosis,tubular atrophy score（ IFTA） and interstitial inflammation of kidney damage were used to evaluate the degree of renal damage. The miR-141 levels in different kidney injuries were analyzed and the relationship between miR-141 levels and prognosis was analyzed according to the median value of miR-141 level. Results QPCR detection showed that the serum miR-141 level of patients with DN was（ 6. 312 ± 1. 804）（ median value of 5. 816）,higher than that of healthy controls（ 1. 247 ± 0. 219）,and the difference was statistically significant（ P〈0. 05）. Serum miR-141 levels in DN patients did not related to sex,age and serum calcium,but were related to BMI,duration of diabetes,proteinuria,fasting plasma glucose,Hb A1 c and e GFR（ P〈0. 05）. The level of serum miR-141 in patients with DN was related to glomerular grading,IFTA and interstitial inflammation,and the level of serum miR-141 and high expression rate increased（ P〈0. 05）as the degree of renal pathological damage increased. Spearman correlation analysis showed that serum miR-141 levels were positively correlated with glomerular grading,IFTA and interstitial inflammation in patients with DN,and the correlation coefficients were 0. 329,0. 226 and 0. 426（P = 0. 000,0. 015 and 0. 000）,respectively. Among 114 cases of DN patients,42 cases of end-stage renal disease occurred during the follow-up period（ ESRD）,the serum level of miR-141 was（ 7. 153 ± 2. 018）,which was higher than 72 cases without ESRD（ 5. 821 ± 1. 775） and the differences were statistically significant（ P〈0. 05）. Compared the low level of miR-141 group,the high level of miR-141 group had an increased risk of 6. 333 folds. Conclusion The elevation of serum miR-141 levels in patients with DN related with DN renal injury and prognosis. The patients with higher miR-141 level presented a more serious renal injury and poor prognosis,and had a certain value in the evaluation of DN disease prediction and prognosis.