血清高迁移率族蛋白B1与糖尿病肾病病人肾功能、炎症因子及氧化应激指标的相关性研究

目的探讨血清高迁移率族蛋白B1(HMGB1)与糖尿病肾病(DN)病人肾功能、炎症因子及氧化应激指标的相关性。方法117例DN病人根据24 h尿白蛋白定量(24hUPQ)分为微量白蛋白尿组(n=55例)和大量白蛋白尿组(n=62例)，同期选择50例单纯2型糖尿病病人作为对照组。检测各组肾功能指标血清肌酐(SCr)、尿素氮(BUN)、肾小球滤过率(GFR)、胱抑素C(Cys-C)]、炎症因子血清核因子κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)、白细胞介素-6(IL-6)]及氧化应激指标丙二醛(MDA)、晚期氧化蛋白产物(AOPP)、超氧化物歧化醇(SOD) 总抗氧化能力(T-AOC)], 并分析血清HMGB1与肾功能、炎症因子及氧化应激指标的相关性。结果大量白蛋白尿组和微量白蛋白尿组病人血清HMGB1表达水平均高于单纯2型糖尿病组，差异有统计学意义(P < 0.05)，而大量白蛋白尿组病人血清HMGB1表达水平高于微量白蛋白尿组，差异有统计学意义(P < 0.05)；各组病人SCr、BUN、GFR、Cys-C等肾功能指标比较差异均有统计学意义(P < 0.01)，单纯2型糖尿病组、微量白蛋白尿组、大量白蛋白尿组病人SCr、BUN、Cys-C依次逐渐升高，而GFR依次逐渐降低(P < 0.01)；各组病人血清NF-κB、TNF-α、ICAM-1、IL-6等炎症因子表达水平比较差异均有统计学意义(P < 0.01)，单纯2型糖尿病组、微量白蛋白尿组、大量白蛋白尿组病人血清NF-κB、TNF-α、ICAM-1、IL-6水平依次逐渐升高(P < 0.01)；各组病人血清MDA、T-AOC、SOD、AOPP等氧化应激指标比较差异均有统计学意义(P < 0.01)，单纯2型糖尿病组、微量白蛋白尿组、大量白蛋白尿组病人血清MDA、AOPP水平依次逐渐升高，而血清T-AOC、SOD水平依次逐渐降低(P < 0.01)；血清HMGB1与肾功能、炎症因子及氧化应激指标呈明显的相关性关系(P < 0.05)。结论DN病人血清HMGB1表达水平随病情严重程度加重而明显升高，与肾功能损伤、炎症及氧化应激反应严重程度存在一定相关性。

Correlation of serum high mobility group protein B1 with renal function,inflammatory factors and oxidative stress in patients with diabetic nephropathy

ObjectiveTo observe the correlation of serum high mobility group protein B1(HMGB1) with renal function, inflammatory factors, oxidative stress of patients with diabetic nephropathy(DN).MethodsOne hundred and seventeen patients with DN were divided into the microalbuminuria group(n=55) and the large albuminuria group(n=62) according to the 24hUPQ, and 50 patients with simple type 2 diabetes mellitus were selected as the control group during the same period.Renal function indexes serum creatinine(SCr), blood urea nitrogen(BUN), glomerlar filtration rate(GFR), cystatin C(Cys-C)], inflammatory factorsnuclear factor-κB(NF-κB), tumor necrosis factor-α(TNF-α), intercellular cell adhesion molecule-1(ICAM-1), interleukin 6(IL-6)] and oxidative stress indicatorsmalondialdehyde(MDA), total antioxygen capability(T-AOC), superoxide dismutase(SOD), advanced oxidation protein products(AOPP)] in each group were measured, and the correlation of serum HMGB1 with renal function, inflammatory factors, oxidative stress indexes were analyzed.ResultsThe serum HMGB1 level in the large albuminuria group and the microalbuminuria group were higher than that in the simple type 2 diabetes mellitus group(P < 0.05), while the serum HMGB1 level of patients in the large albuminuria group was higher than that in the microalbuminuria group(P < 0.05).There was a statistically significant difference in three groups between the renal indicators such as SCr, BUN, GFR, Cys-C(P < 0.01), and the SCr, BUN, Cys-C in the simple type 2 diabetes mellitus group, the microalbuminuria group and the large albuminuria group gradually increased, but the GFR gradually decrease(P < 0.01).There was a statistically significant difference in the levels of serum NF-κB, TNF-α, ICAM-1, IL-6 in three groups (P < 0.01).The levels of NF-κB, TNF-α, ICAM-1 and IL-6 in the simple type 2 diabetes mellitus group, the microalbuminuria group and the large albuminuria group gradually increased(P < 0.01).There was a statistically significant difference in three groups between the oxidative stress indicators such as MDA, T-AOC, SOD, AOPP(P < 0.01).The serum MDA and AOPP levels in simple type 2 diabetes mellitus group, microalbuminuria group and the large albuminuria group gradually increased, but the serum T-AOC and SOD levels gradually decreased(P < 0.01).Serum HMGB1 was significantly correlated with renal function, inflammatory factors and oxidative stress indicators(P < 0.05).ConclusionsThe level of serum HMGB1 in DN patients is increased significantly with the aggravation of disease severity, which is related to the injury of renal function, inflammation and the severity of oxidative stress reaction.