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

Yanqing CHI; Tao ZHANG; Yingli KANG; Ke YU; Maodong LIU; Ying LI

doi:10.16016/j.1000-5404.201903174

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

Basic Medicine | 更新时间：2026-01-09

- Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
- Journal of Third Military Medical University Vol. 41, Issue 16, Pages: 1545-1551(2019)
- 作者机构：
  
  050051 石家庄，河北医科大学第三医院肾内科，河北省肾脏病研究中心
- 作者简介：
- 基金信息：
  
  the Research and Development Program for Young Scientists of Chinese Medical Association Nephrology Branch(13030410426)
- DOI：10.16016/j.1000-5404.201903174
  CLC： R364.12; R699.2; R977.9
- Received：21 March 2019，
  
  Revised：2019-04-17，
  
  Published：30 August 2019
- 稿件说明：
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Yanqing CHI, Tao ZHANG, Yingli KANG, et al. Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats[J]. Journal of Third Military Medical University, 2019, 41(16): 1545-1551.
DOI：

Yanqing CHI, Tao ZHANG, Yingli KANG, et al. Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats[J]. Journal of Third Military Medical University, 2019, 41(16): 1545-1551. DOI： 10.16016/j.1000-5404.201903174.

摘要

目的

探讨氨基甲酰促红细胞生成素(carbamoyl-erythropoietin

CEPO)对大鼠肾脏及人肾小管上皮细胞(HK-2)缺血再灌注损伤的保护作用。

方法

构建SD大鼠肾脏缺血再灌注肾损伤模型，造模后0、24、48 h按照5 000 U/kg的剂量向腹腔内注射促红细胞生成素(EPO)或者CEPO，与肾脏缺血再灌注肾损伤模型组和假手术组进行对比分析，观察各组大鼠血清尿素氮(BUN)、血肌酐(Scr)、红细胞比容(Hct)，肾组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)，血清中IL-6、IL-10变化，肾组织PAS染色观察肾脏病理改变。对HK-2细胞进行缺血再灌注损伤处理，同时给予EPO和CEPO干预处理，实时定量RT-PCR检测IL-6、IL-10、TNF-α mRNA表达，Western blot检测IL-6、IL-10和凋亡相关蛋白cleaved-Caspase 3的蛋白表达。

结果

在大鼠肾脏缺血再灌注模型中，EPO或者CEPO干预治疗后，大鼠Scr、BUN水平明显降低；血清中促炎因子IL-6水平明显降低，抗炎因子IL-10水平明显提升；肾组织匀浆中MDA、TNF-α水平明显降低，SOD水平明显升高(

0.05)；PAS染色显示肾损伤明显减轻，且CEPO较EPO能起到更好的效果，CEPO治疗组Hct升高较EPO治疗组更加缓和(

05)。HK-2细胞缺血再灌注模型中，EPO和CEPO能降低缺血再灌注HK-2细胞内TNF-α和IL-6 mRNA的表达，增加IL-10 mRNA和蛋白的表达，降低IL-6和cleaved-Caspase 3蛋白的表达，且CEPO能显示出更好的效果(

0.05)。

结论

CEPO可能通过减轻炎症和减少凋亡发挥缓解缺血再灌注对肾脏的损伤作用，并且相对EPO能减轻Hct升高的副作用。

Abstract

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

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 (

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 (

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 p

rotein 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 (

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.

关键词

Keywords

references

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