去唾液红细胞生成素对糖尿病小鼠缺血再灌注诱导的急性肾损伤的肾保护作用。
Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia-reperfusion-induced acute kidney injury.
机构信息
Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
出版信息
Nephrology (Carlton). 2010 Feb;15(1):93-101. doi: 10.1111/j.1440-1797.2009.01170.x.
AIM
Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non-haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes-related acceleration of renal damage after ischaemia-reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non-haematopoietic erythropoietin derivative, against ischaemia-reperfusion-induced acute kidney injury in diabetic mice.
METHODS
C57BL/6J mice with and without streptozotocin-induced diabetes were subjected to 30 min unilateral renal ischaemia-reperfusion injury at 1 week after induction of diabetes. They were divided into four group: (i) non-diabetic plus ischaemia-reperfusion injury; (ii) non-diabetic plus ischaemia-reperfusion injury plus asialoerythropoietin (3000 IU/kg bodyweight); (iii) diabetic plus ischaemia-reperfusion injury; and (iv) diabetic plus ischemia-reperfusion injury plus asialoerythropoietin. Experiments were conducted at the indicated time periods after ischaemia-reperfusion injury.
RESULTS
Ischaemia-reperfusion injury of diabetic kidney resulted in significantly low protein expression levels of bcl-2, an anti-apoptotic molecule, and bone morphogenetic protein-7 (BMP-7), an anti-fibrotic and pro-regenerative factor, compared with non-diabetic kidneys. Diabetic kidney subsequently showed severe damage including increased tubular cell apoptosis, tubulointerstitial fibrosis and decreased tubular proliferation, compared with non-diabetic kidney. Treatment with asialoerythropoietin induced bcl-2 and BMP-7 expression in diabetic kidney and decreased tubular cell apoptosis, tubulointerstitial fibrosis and accelerated tubular proliferation.
CONCLUSION
Reduced induction bcl-2 and BMP-7 may play a role in the acceleration of renal damage after ischaemia-reperfusion injury in diabetic kidney. The renoprotective effects of asialoerythropoietin on acute kidney injury may be mediated through the induction of bcl-2 and BMP-7.
目的
糖尿病患者在急性肾损伤后恢复失败的风险更高，但机制和治疗策略仍不清楚。红细胞生成素在各种非造血细胞中具有细胞保护作用。本研究旨在阐明糖尿病相关的肾损伤加速缺血再灌注损伤的机制，并研究非造血红细胞生成素衍生物去唾液酸红细胞生成素治疗糖尿病小鼠缺血再灌注诱导的急性肾损伤的治疗潜力。
方法
在诱导糖尿病后 1 周，对 C57BL/6J 小鼠进行链脲佐菌素诱导的糖尿病和单侧肾缺血再灌注损伤 30 分钟。将它们分为四组：（i）非糖尿病加缺血再灌注损伤；（ii）非糖尿病加缺血再灌注损伤加去唾液酸红细胞生成素（3000 IU/kg 体重）；（iii）糖尿病加缺血再灌注损伤；和（iv）糖尿病加缺血再灌注损伤加去唾液酸红细胞生成素。在缺血再灌注损伤后，在指定的时间点进行实验。
结果
与非糖尿病肾脏相比，糖尿病肾脏的缺血再灌注损伤导致抗凋亡分子 bcl-2 和骨形态发生蛋白-7（BMP-7）的蛋白表达水平显著降低，BMP-7 是一种抗纤维化和促再生因子。与非糖尿病肾脏相比，糖尿病肾脏随后表现出严重的损伤，包括肾小管细胞凋亡增加、肾小管间质纤维化和管状增殖减少。用去唾液酸红细胞生成素治疗可诱导糖尿病肾脏中 bcl-2 和 BMP-7 的表达，并减少肾小管细胞凋亡、肾小管间质纤维化和加速管状增殖。
结论
bcl-2 和 BMP-7 的诱导减少可能在糖尿病肾脏缺血再灌注损伤后肾损伤的加速中起作用。去唾液酸红细胞生成素对急性肾损伤的肾保护作用可能是通过诱导 bcl-2 和 BMP-7 介导的。
Zotero 插件