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

Correlation between serum miR-133b level and renal injury and prognosis in the elderly with diabetic nephropathy

摘要:

目的 探讨血清微小核糖核酸-133b(miR-133b)水平与老年糖尿病肾病(DN)患者肾脏损伤及预后的关系。方法 入选2016年1月至2017年12月海南省人民医院肾病风湿科收治的182例老年DN患者(DN组)及同期来本院进行体检的80名健康人群(对照组),比较2组miR-133b水平及其水平与老年DN患者不同临床指标的关系。采用肾病分级、间质性纤维化和小管萎缩(IFTA)评分、间质炎症来评价肾脏损伤情况,分析不同肾脏损伤程度和miR-133b水平的相关性。根据DN组miR-133b水平平均值将182例患者分为低表达组与高表达组,分析2组miR-133b水平与患者预后的关系。利用2-△△Ct法计算miR-133b的相对表达水平。采用SPSS 19.0统计软件对数据进行分析,根据数据类型,组间比较采用单因素方差分析、成组t检验或χ²检验。相关性分析采用Pearson法。结果 DN组血清miR-133b水平显著高于对照组,差异有统计学意义[(5.38±1.28) vs (1.06±0.25),P<0.01]。不同的糖尿病病程、24 h尿蛋白定量、血肌酐(SCr)、血尿素氮(BUN)及估算肾小球滤过率(eGFR)间血清miR-133b水平比较,差异均有统计学意义(P<0.05)。不同肾病分级、IFTA评分及间质炎症分级间血清miR-133b水平比较,差异亦有统计学意义(P<0.05),且随着肾脏病理损伤程度的增加,血清miR-133b水平显著升高(P<0.05)。Pearson相关分析显示,患者血清miR-133b水平与24 h尿蛋白定量、SCr、BUN、肾病分级、IFTA及间质炎症呈正相关(r分别为0.492、0.382、0.415、0.463、0.338、0.547,P<0.01),与eGFR水平呈负相关(r=-0.625,P<0.01)。182例老年DN患者最终有76例发展为终末期肾病(ESRD),其中miR-133b高表达组(65.9%,58/88)相对于低表达组(19.1%,18/94)发展为ESRD的比例显著增加(χ²=6.175,P=0.006)。结论 血清miR-133b水平在老年DN患者中明显增高,且与老年DN患者肾脏损伤及预后不良有关,miR-133b水平较高的患者肾脏损伤程度较严重且预后较差。

Abstract:

Objective To investigate the relationship of serum miR-133b level with renal injury and prognosis in the elderly with diabetic nephropathy (DN). Methods A total of 182 elderly DN patients (DN group) admitted to our hospital from January 2016 to December 2017 were enrolled in this study, and another 80 matched healthy individuals taking physical examination during the same period served as control group. Real-time quantitative PCR (qRT-PCR) was used to detect serum miR-133b level, and the results were analyzed for the relationship with clinical indices in the elderly DN patients. Renal injury was evaluated by nephrotic grade, interstitial fibrosis and tubular atrophy (IFTA) score and interstitial inflammation, and the diversity of miR-133b level in different severity grades was analyzed. After the DN patients were divided into low- and high-expressed miR-133b groups, and the relationship of miR-133b level with pronostic in the two groups was also analyzed. SPSS statistics 19.0 was used to perform the statistical analysis. One-way analysis of variance, group t test, or Chi-square test was employed for intergroup comparison based on different data types. Pearson correlation analysis was performed for the correlations. Results The serum miR-133b level was significantly higher in the DN group than in the control group [(5.38±1.28) vs (1.06±0.25), P<0.01]. Significant differences were also seen in its serum level among the patients with different course of diabetes, proteinuria, serum creatinine (SCr), blood urea nitrogen (BUN) and estimated glomerularfiltration rate (eGFR) (P<0.05), and so were in those with different nephrotic grades, IFTA score and interstitial inflammation (P<0.05). What′s more, with the severity of renal pathological damage, the serum level was elevated (P<0.05). Pearson correlation analysis showed that the serum miR-133b level was positively correlated with proteinuria, SCr and BUN levels, nephrotic grade, IFTA score, and interstitial inflammation (r=0.492, 0.382,0.415,0.463,0.338,0.547, P<0.01), but negatively correlated with eGFR level (r=-0.625, P<0.01). Among the 182 elderly DN patients, 76 developed into end-stage renal disease (ESRD), with 65.9%(58/88) from the high miR-133b expression group while 19.1%(18/94) from the low expression group, indicating the former group having higher risk of ESRD (χ²=6.175, P=0.006). Conclusion Serum miR-133b level is significantly elevated, and associated with renal injury and poor prognosis in the elderly DN patients. The higher the level is, the severer the renal injury is and the poorer the prognosis is.