2型糖尿病肾病血清LOX-1、TIMP3水平与肾功能的关系及诊断价值

Relationship between serum LOX-1 and TIMP3 levels and renal function in type 2 diabetic nephropathy and their diagnostic value

目的探讨血清凝集素样氧化低密度脂蛋白受体1(LOX-1)、基质金属蛋白酶抑制因子3(TIMP3)与2型糖尿病肾病(T2DN)患者肾功能的相关性及对T2DN的诊断价值。方法选择2019年3月至2021年12月该院收治的T2DN患者117例作为观察对象(DN组),根据尿微量清蛋白/肌酐比值(ACR),将T2DM患者分为微量蛋白尿组50例(ACR:30~300 mg/g),大量蛋白尿组67例(ACR>300 mg/g),另选取同期单纯2型糖尿病(T2DM)患者118例作为T2DM组(ACR<30 mg/g),另选择同期体检健康者120例作为对照组,采用酶联免疫吸附试验(ELISA)检测血清LOX-1、TIMP3水平。Pearson法分析血清LOX-1、TIMP3水平与肾功能指标相关性;多元逐步线性回归法分析血清LOX-1、TIMP3的影响因素;绘制受试者工作特征(ROC)曲线分析血清LOX-1、TIMP3对T2DN的诊断价值。结果与对照组和T2DM组比较,DN组患者血清LOX-1水平显著升高,TIMP3水平显著降低,差异有统计学意义(P<0.05),T2DM组血清LOX-1水平高于对照组,TIMP3水平低于对照组,差异有统计学意义(P<0.05);与微量蛋白尿组比较,大量蛋白尿组T2DN患者血清LOX-1水平显著升高,TIMP3水平显著降低,差异有统计学意义(P<0.05);相关性分析显示,T2DN患者血清LOX-1与胱抑素C(CysC)、尿素氮(BUN)、β2-微球蛋白(β2-MG)、肌酐(SCr)呈正相关,与肾小球滤过率(eGFR)呈负相关(P<0.05),血清TIMP3水平与CysC、BUN、β2-MG、SCr呈负相关,与eGFR呈正相关(P<0.05);多元线性回归分析显示,CysC、BUN、β2-MG、SCr、eGFR是血清TIMP3、LOX-1的独立影响因素(P<0.05);血清LOX-1、TIMP3联合诊断T2DN的灵敏度为84.62%,特异度为84.75%,曲线下面积(AUC)为0.901(95%CI:0.855~0.936)。结论T2DN患者血清LOX-1水平升高、TIMP3水平降低,且与T2DN严重程度有关,二者联合对T2DN有一定诊断价值。

Objective To investigate the correlation between serum lectin-like oxidized low-density lipoprotein receptor 1(LOX-1),inhibitor of matrix metalloproteinase 3(TIMP3)and renal function in patients with type 2 diabetic nephropathy(T2DN)and their diagnostic value for T2DN.Methods A total of 117 T2DN patients admitted to the hospital from March 2019 to December 2021 were regarded as observation objects(DN group).According to the urine microalbumin/creatinine ratio(ACR),the patients were grouped into the microalbuminuria group with 50 cases(ACR:30-300 mg/g)and the macroalbuminuria group with 67 cases(ACR>300 mg/g).Another 118 patients with simple type 2 diabetes mellitus(T2DM)were taken as the T2DM group(ACR<30 mg/g).Meantime,120 healthy people were taken as the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of serum LOX-1 and TIMP3.Pearson method was applied to analyze the correlation between the levels of serum LOX-1 and TIMP3 and renal function indexes.The influencing factors of serum LOX-1 and TIMP3 were analyzed by multiple stepwise linear regression.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum LOX-1 and TIMP3 for T2DN.Results Compared with the control group and T2DM group,the level of serum LOX-1 in the DN group was greatly increased,the level of TIMP3 was greatly decreased,and the differences were statistically significant(P<0.05).The serum LOX-1 level in T2DM group was higher than that in the control group,the serum TIMP3 level was lower than that in the control group,and the differences were statistically significant(P<0.05).Compared with the microalbuminuria group,the level of serum LOX-1 of the T2DN patients in the macroalbuminuria group was greatly increased,the level of TIMP3 was greatly decreased,and the differences were statistically significant(P<0.05).Correlation analysis showed that serum LOX-1 in T2DN patients was positively correlated with CystatinC(CysC),Blood urea nitrogen(BUN),β2-microglobulin(β2-MG)and creatinine(SCr),and negatively correlated with glomerular filtration rate(eGFR)(P<0.05),and the level of serum TIMP3 was negatively correlated with CysC,BUN,β2-MG,SCr,and positively correlated with eGFR(P<0.05).Multiple linear regression analysis showed that CysC,BUN,β2-MG,SCr and eGFR were independent influencing factors of serum TIMP3 and LOX-1(P<0.05).The sensitivity of serum LOX-1 combined TIMP3 to diagnose T2DN was 84.62%,the specificity was 84.75%,and the area under the curve(AUC)was 0.901(95%CI:0.855-0.936).Conclusion Serum LOX-1 level is increased and TIMP3 level is decreased in T2DN patients,and they are related to the severity of T2DN.The combination of the two has certain diagnostic value for T2DN.