Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia-reperfusion-induced acute kidney injury

被引：21

作者：

Nakazawa, Jun ^{[1
]}

Isshiki, Keiji ^{[1
]}

Sugimoto, Toshiro ^{[1
]}

Araki, Shin-Ichi ^{[1
]}

Kume, Shinji ^{[1
]}

Yokomaku, Yukiyo ^{[1
]}

Chin-Kanasaki, Masami ^{[1
]}

Sakaguchi, Masayoshi ^{[1
]}

Koya, Daisuke ^{[2
]}

Haneda, Masakazu ^{[3
]}

Kashiwagi, Atsunori ^{[1
]}

Uzu, Takashi ^{[1
]}

机构：

[1] Shiga Univ Med Sci, Dept Med, Shiga 5202192, Japan

[2] Kanazawa Med Univ, Div Endocrinol & Metab, Kanazawa, Ishikawa, Japan

[3] Asahikawa Med Coll, Div Metab & Biosyst Sci, Asahikawa, Hokkaido 078, Japan

来源：

NEPHROLOGY | 2010年 / 15卷 / 01期

关键词：

acute tubular necrosis; apoptosis; bone morphogenetic protein; erythropoietin; fibrosis; ischaemia-reperfusion; ACUTE-RENAL-FAILURE; BONE MORPHOGENIC PROTEIN-7; GROWTH-FACTOR-I; ERYTHROPOIETIN RECEPTORS; N-ACETYLCYSTEINE; RAT-KIDNEY; NEPHROPATHY; APOPTOSIS; SURVIVAL; CELLS;

D O I：

10.1111/j.1440-1797.2009.01170.x

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：93 / 101

页数：9

共 27 条

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