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1型糖尿病患者中促纤维化和抗纤维化生长因子的尿排泄:与糖尿病肾病的相互关系

[Urinary excretion of fibrogenic and antifibrotic growth factors in type 1 diabetic patients: the interrelationship with diabetic nephropathy].

作者信息

Bondar' I A, Klimontov V V, Parfent'eva E M, Romanov V V, Nadeev A P

出版信息

Ter Arkh. 2012;84(6):36-40.

PMID:22997916
Abstract

AIM

To assess the relation between urinary excretion of profibrotic and antifibrotic growth factors, albuminuria and glomerular fibrosis in type 1 diabetic patients.

MATERIALS AND METHODS

64 patients with diabetes were examined, including 25 ones with normal albumin excretion rate (AER), 30 microalbuminuric and 9 macroalbuminuric patients. Urinary excretion of type IV collagen, transforming growth factor-beta 1] (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF) and bone morphogenetic protein-7 (BMP-7) was determined by ELISA and compared to control (10 healthy subjects). Renal biopsy specimens were assessed in 7 patients with normal AER and in 14 microalbuminuric patients.

RESULTS

Type IV collagen, TGF-beta1 and TNF-alpha excretion was increased significantly in patients with micro- and macroalbuminuria as compared to control (all p<0.05). Excretion of FGF-2 was increased in macroalbuminuric patients only (p=0.003). No marked changes in excretion of antifibrotic growth factors (HGF and BMP-7) were observed. TNF-alpha and FGF-2 correlated positively with urinary type IV collagen (r=0.37 and r=0.31, respectively). The presence of glomerular fibrosis in renal biopsy specimens was associated with higher excretion of TGF-beta1, TNF-alpha and FGF-2 (all p<0.05).

CONCLUSION

The results suggest that unbalance between profibrotic and antifibrotic growth factors in the kidneys plays an important role in pathogenesis of diabetic nephropathy. Urinary TGF-beta1, TNF-alpha and FGF-2 may offer new possibilities for detection of renal fibrosis in diabetic patients.

摘要

目的

评估1型糖尿病患者促纤维化和抗纤维化生长因子的尿排泄、蛋白尿与肾小球纤维化之间的关系。

材料与方法

对64例糖尿病患者进行检查,其中25例白蛋白排泄率(AER)正常,30例微量白蛋白尿患者和9例大量白蛋白尿患者。采用酶联免疫吸附测定法(ELISA)测定IV型胶原、转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、成纤维细胞生长因子-2(FGF-2)、肝细胞生长因子(HGF)和骨形态发生蛋白-7(BMP-7)的尿排泄情况,并与对照组(10名健康受试者)进行比较。对7例AER正常的患者和14例微量白蛋白尿患者的肾活检标本进行评估。

结果

与对照组相比,微量和大量白蛋白尿患者的IV型胶原、TGF-β1和TNF-α排泄显著增加(均p<0.05)。仅大量白蛋白尿患者的FGF-2排泄增加(p=0.003)。未观察到抗纤维化生长因子(HGF和BMP-7)排泄的明显变化。TNF-α和FGF-2与尿IV型胶原呈正相关(r分别为0.37和0.31)。肾活检标本中肾小球纤维化的存在与TGF-β1、TNF-α和FGF-2的较高排泄相关(均p<0.05)。

结论

结果表明,肾脏中促纤维化和抗纤维化生长因子之间的失衡在糖尿病肾病的发病机制中起重要作用。尿TGF-β1、TNF-α和FGF-2可能为糖尿病患者肾纤维化的检测提供新的可能性。

相似文献

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[Urinary excretion of fibrogenic and antifibrotic growth factors in type 1 diabetic patients: the interrelationship with diabetic nephropathy].1型糖尿病患者中促纤维化和抗纤维化生长因子的尿排泄:与糖尿病肾病的相互关系
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