Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats

Objective To investigate the protective effect of carbamoyl-erythropoietin (CEPO) against ischemia-reperfusion (IR) injury in rat kidneys and in human renal tubular epithelial cells (HK-2). Methods In a SD rat model of renal IR injury, EPO or CEPO was intraperitoneally injected at the dose of 5 000...

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Main Authors: CHI Yanqing, ZHANG Tao, KANG Yingli, YU Ke, LIU Maodong, LI Ying
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2019-08-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/201903174.htm
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author CHI Yanqing
ZHANG Tao
KANG Yingli
YU Ke
LIU Maodong
LI Ying
author_facet CHI Yanqing
ZHANG Tao
KANG Yingli
YU Ke
LIU Maodong
LI Ying
author_sort CHI Yanqing
collection DOAJ
description Objective To investigate the protective effect of carbamoyl-erythropoietin (CEPO) against ischemia-reperfusion (IR) injury in rat kidneys and in human renal tubular epithelial cells (HK-2). Methods In a SD rat model of renal IR injury, EPO or CEPO was intraperitoneally injected at the dose of 5 000 U/kg at 0, 24, and 48 h after renal IR. Serum levels of urea nitrogen (BUN) and creatinine (Scr), hematocrit (Hct), and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in the kidney homogenate were detected; serum levels of interleukin-6 (IL-6) and IL-10 were detected and PAS staining was used for assessment of the renal pathologies. HK-2 cells were exposed to IR injury and treated with EPO or CEPO, and the mRNA expressions of IL-6, IL-10, and TNF-α were detected using Real-time PCR; the protein expressions of IL-6, IL-10, and cleaved Caspase-3 were analyzed with Western blotting. Results In the rat model of renal IR injury, Scr, BUN and IL-6 levels were reduced and serum IL-10 level was increased significantly after treatment with EPO or CEPO, which also significantly lowered the levels of MDA and TNF-α and increased SOD levels in the kidney homogenate (P < 0.05). PAS staining showed a significant improvement of renal pathological damages after the treatments, and the effect was more obvious with CEPO. CEPO treatment resulted in a milder increase in Hct as compared with EPO (P < 0.05). In HK-2 cells with IR injury, both EPO and CEPO treatment reduced the mRNA expressions of TNF-α and IL-6, increased the mRNA and protein expressions of IL-10, and reduced the protein expressions of IL-10 and cleaved Caspase-3, and these effects were significantly more obvious with CEPO than with EPO treatment (P < 0.05). Conclusion CEPO can alleviate renal IR injury in rats by reducing inflammation and apoptosis, and can more effectively suppress the elevation of Hct than EPO in the rat models.
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spelling doaj.art-d80e5cae3e13472b8dcf278d962be8292022-12-21T22:48:18ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042019-08-0141161545155110.16016/j.1000-5404.201903174Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in ratsCHI Yanqing0ZHANG Tao1KANG Yingli2YU Ke3LIU Maodong4LI Ying5Department of Nephrology, Hebei Provincial Research Center for Kidney Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, ChinaDepartment of Nephrology, Hebei Provincial Research Center for Kidney Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, ChinaDepartment of Nephrology, Hebei Provincial Research Center for Kidney Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, ChinaDepartment of Nephrology, Hebei Provincial Research Center for Kidney Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, ChinaDepartment of Nephrology, Hebei Provincial Research Center for Kidney Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, ChinaDepartment of Nephrology, Hebei Provincial Research Center for Kidney Diseases, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, ChinaObjective To investigate the protective effect of carbamoyl-erythropoietin (CEPO) against ischemia-reperfusion (IR) injury in rat kidneys and in human renal tubular epithelial cells (HK-2). Methods In a SD rat model of renal IR injury, EPO or CEPO was intraperitoneally injected at the dose of 5 000 U/kg at 0, 24, and 48 h after renal IR. Serum levels of urea nitrogen (BUN) and creatinine (Scr), hematocrit (Hct), and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in the kidney homogenate were detected; serum levels of interleukin-6 (IL-6) and IL-10 were detected and PAS staining was used for assessment of the renal pathologies. HK-2 cells were exposed to IR injury and treated with EPO or CEPO, and the mRNA expressions of IL-6, IL-10, and TNF-α were detected using Real-time PCR; the protein expressions of IL-6, IL-10, and cleaved Caspase-3 were analyzed with Western blotting. Results In the rat model of renal IR injury, Scr, BUN and IL-6 levels were reduced and serum IL-10 level was increased significantly after treatment with EPO or CEPO, which also significantly lowered the levels of MDA and TNF-α and increased SOD levels in the kidney homogenate (P < 0.05). PAS staining showed a significant improvement of renal pathological damages after the treatments, and the effect was more obvious with CEPO. CEPO treatment resulted in a milder increase in Hct as compared with EPO (P < 0.05). In HK-2 cells with IR injury, both EPO and CEPO treatment reduced the mRNA expressions of TNF-α and IL-6, increased the mRNA and protein expressions of IL-10, and reduced the protein expressions of IL-10 and cleaved Caspase-3, and these effects were significantly more obvious with CEPO than with EPO treatment (P < 0.05). Conclusion CEPO can alleviate renal IR injury in rats by reducing inflammation and apoptosis, and can more effectively suppress the elevation of Hct than EPO in the rat models.http://aammt.tmmu.edu.cn/Upload/rhtml/201903174.htmcarbamoylated erythropoietinrenal ischemia-reperfusion injuryacute kidney injury
spellingShingle CHI Yanqing
ZHANG Tao
KANG Yingli
YU Ke
LIU Maodong
LI Ying
Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
Di-san junyi daxue xuebao
carbamoylated erythropoietin
renal ischemia-reperfusion injury
acute kidney injury
title Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
title_full Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
title_fullStr Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
title_full_unstemmed Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
title_short Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
title_sort protective effect of carbamoylated erythropoietin against renal ischemia reperfusion injury in rats
topic carbamoylated erythropoietin
renal ischemia-reperfusion injury
acute kidney injury
url http://aammt.tmmu.edu.cn/Upload/rhtml/201903174.htm
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