Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Int Urol Nephrol. 2010 Jun;42(2):487-92. doi: 10.1007/s11255-009-9643-9. Epub 2009 Sep 19.
The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-beta (TGF-beta) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-beta by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-beta in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AER > or = 300 mg/24 h) and 66 patients with normoalbuminuria (AER < or = 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-beta were determined. Ox-LDL and TGF-beta were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 + or - 3.99 vs. 72.45 + or - 2.48 U/l; P < 0.001 and 6.46 + or - 0.74 vs. 2.49 + or - 0.39 ng/ml; P < 0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-beta (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P < 0.05) and TGF-beta (r = 0.306; P < 0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-beta (ox-LDL), attenuated the association of ox-LDL (TGF-beta) with AER. In conclusion, this study demonstrated the association of TGF-beta and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-beta and ox-LDL.
糖尿病肾病的发病机制主要表现为大量白蛋白尿,但目前仍知之甚少。有报道称转化生长因子-β(TGF-β)在此过程中发挥关键作用。体外研究表明,给予氧化型低密度脂蛋白(ox-LDL)可导致人肾小球系膜细胞中 TGF-β表达上调。本研究旨在评估糖尿病患者大量白蛋白尿、ox-LDL 与 TGF-β之间的关系。共纳入 77 例白蛋白排泄率(AER)≥300mg/24h 的大量白蛋白尿(macroalbuminuria)2 型糖尿病患者和 66 例 AER≤30mg/24h 的正常白蛋白尿患者。抽取空腹血样,检测血清 ox-LDL 和 TGF-β水平。结果发现,大量白蛋白尿患者 ox-LDL 和 TGF-β显著高于正常白蛋白尿患者(98.93±3.99 vs. 72.45±2.48 U/l;P<0.001 和 6.46±0.74 vs. 2.49±0.39 ng/ml;P<0.001)。大量白蛋白尿患者 ox-LDL 与 TGF-β呈显著正相关(r=0.376;P<0.01)。AER 与 ox-LDL(r=0.302;P<0.05)和 TGF-β(r=0.306;P<0.05)在大量白蛋白尿患者中呈显著相关。校正潜在混杂因素后,这种相关性仍然显著。校正 TGF-β(ox-LDL)后,ox-LDL(TGF-β)与 AER 的相关性减弱。总之,本研究表明 TGF-β和 ox-LDL 与大量白蛋白尿 2 型糖尿病患者的蛋白尿相关,并提示这种关系高度介导于 TGF-β与 ox-LDL 之间的相关性。