당뇨병 신증을 동반한 환자에서 단핵구 내 NF-кB 및 AP - 1의 활성화

Abstract

Background We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC).

Methods From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and 49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-β1 (transforming growth factor-β1), and 24-hour urinary albumin excretion (UAE) were measured.

Results Spontaneous ROS was significantly higher in group III and II than group I (60.7 ± 3.3 vs. 60.0 ± 3.0 vs. 41.1 ± 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 ± 2.2 vs. 11.1 ± 2.0%, respectively; increment of PMA-induced ROS production 23.5 ± 4.5 vs. 21.6 ± 2.2%, respectively). The activities of NF-κB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-β1 levels were higher in Group III than Group II (3.23 ± 0.39 vs. 1.99 ± 0.68 ng/mg in PBMCs, 16.88 ± 6.84 vs. 5.61 ± 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-κB and AP-1 and 24-hour UAE.

Conclusion Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-κB and AP-1, but not Sp1, and increased expression of TGF-β1.