IgA肾病患者血清miR-155、SOCS-1水平与肾间质纤维化的相关性

Correlation between serum miR-155,SOCS-1 levels and renal interstitial fibrosis in patients with IgA nephropathy

目的探究IgA肾病患者血清微小核糖核酸-155(miR-155)、细胞因子信号转导抑制因子-1(SOCS-1)水平变化及其与肾间质纤维化的关系。方法选取2009年1月至2018年6月济宁市第一人民医院收治的365例原发性IgA肾病患者作为研究对象,根据肾间质纤维化程度将入组患者分为T0组139例、T1组124例、T2组102例。另选取同期在本院体检的健康者361例作为健康对照组。采用实时荧光定量PCR(qRT-PCR)技术检测研究对象的血清miR-155表达水平,采用酶联免疫吸附(ELISA)法检测血清SOCS-1、转化生长因子-β1(TGF-β1)、单核细胞趋化蛋白1(MCP-1)表达水平。采用logistic回归模型分析IgA肾病患者肾间质纤维化发生的影响因素;采用Pearson法分析IgA肾病患者血清miR-155、SOCS-1水平与肾间质纤维化发生影响因素、TGF-β1、MCP-1相关性;采用受试者工作特征(ROC)曲线分析血清miR-155、SOCS-1水平对IgA肾病患者肾间质纤维化发生的预测价值。结果健康对照组、T0组、T1组、T2组SBP、DBP、24 h尿蛋白定量、血肌酐、血尿酸水平及血清miR-155、TGF-β1、MCP-1、尿视黄醇结合蛋白(RBP)、乙酰βD氨基葡萄糖苷酶(NAG)水平依次显著升高,血红蛋白、eGFR、尿渗透压及血清SOCS-1水平依次显著降低(均P<0.05)。高SBP、高DBP、低血红蛋白、高血肌酐、高尿酸、高24 h尿蛋白定量、低eGFR水平是影响IgA肾病患者肾间质纤维化发生的独立危险因素(均P<0.05)。IgA肾病患者血清miR-155水平与TGF-β1、MCP-1、SBP、DBP、血肌酐、血尿酸水平及24 h尿蛋白定量呈正相关,与SOCS-1、血红蛋白、eGFR水平呈负相关(均P<0.05)。血清SOCS-1水平与TGF-β1、MCP-1、SBP、DBP、血肌酐、血尿酸水平及24 h尿蛋白定量呈负相关,与血红蛋白、eGFR水平呈正相关(均P<0.05)。血清miR-155、SOCS-1水平联合检测预测IgA肾病患者肾间质纤维化发生的曲线下面积为0.882,明显大于血清miR-155、SOCS-1水平单独检测(均P<0.05)。结论IgA肾病患者血清miR-155表达上调、SOCS-1表达下调,可能作为预测因子,对肾间质纤维化发生具有一定评估价值。

Objective To investigate the changes of serum micro ribonucleic acid-155(miR-155)and suppressor of cytokine signaling-1(SOCS-1)levels in patients with IgA nephropathy and their relationship with renal interstitial fibrosis.Methods A total of 365 patients with primary IgA nephropathy admitted to Jining First People's Hospital from January 2009 to June 2018 were selected as the research objects.According to the degree of renal interstitial fibrosis,the patients were divided into T0 group(139 cases),T1 group(124 cases)and T2 group(102 cases).In addition,361 healthy subjects who had physical examination in our hospital in the same period were selected as the healthy control group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression level of miR-155 in serum of all the subjects;the levels of serum SOCS-1,transforming growth factor-β1(TGF-β1)and monocyte chemoattractant protein-1(MCP-1)were detected by enzyme-linked immunosorbent assay(ELISA).Logistic regression model was used to analyze the influencing factors of renal interstitial fibrosis in patients with IgA nephropathy;Pearson method was used to analyze the correlation between serum miR-155,SOCS-1 levels and influencing factors of renal interstitial fibrosis,TGF-β1 and MCP-1;receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum miR-155 and SOCS-1 levels in patients with IgA nephropathy.Results The levels of systolic blood pressure(SBP),diastolic blood pressure(DBP),24 h urine protein,serum creatinine,serum uric acid,miR-155,TGF-β1,MCP-1,urinary retinol binding protein(RBP)and acetylβD-glucosaminidase(NAG)in healthy control group,T0 group,T1 group and T2 group were significantly increased in turn,while the levels of hemoglobin,estimated glomerular filtration rate(eGFR),urinary osmotic pressure and serum SOCS-1 were significantly decreased in turn(all P<0.05).High SBP,high DBP,low hemoglobin,high serum creatinine,high uric acid,high 24-hour urine protein and low eGFR level were independent risk factors of renal interstitial fibrosis in patients with IgA nephropathy(all P<0.05).The serum miR-155 level was positively correlated with TGF-β1,MCP-1,SBP,DBP,serum creatinine,serum uric acid levels and 24 h urine protein,but negatively correlated with SOCS-1,hemoglobin and eGFR levels(all P<0.05).The serum SOCS-1 level was negatively correlated with TGF-β1,MCP-1,SBP,DBP,serum creatinine,uric acid levels and 24 h urine protein,but positively correlated with hemoglobin and eGFR levels(all P<0.05).The area under the curve of predicting the occurrence of renal interstitial fibrosis in patients with IgA nephropathy by serum miR-155 and SOCS-1 combined detection was 0.882,which was significantly larger than that by serum miR-155 and SOCS-1 alone(P<0.05).Conclusions The expression of miR-155 is up-regulated and SOCS-1 is down-regulated in IgA nephropathy patients,they may be used as predictors to evaluate the occurrence of renal interstitial fibrosis.