促红细胞生成素对横纹肌溶解致大鼠急性肾损伤时内质网应激相关蛋白的影响

基础医学与临床 ›› 2016, Vol. 36 ›› Issue (9): 1268-1273.

促红细胞生成素对横纹肌溶解致大鼠急性肾损伤时内质网应激相关蛋白的影响

耿兴华¹,李建东²,刘圣君³

1. 河北北方学院研究生部
2. 河北北方学院
3. 河北北方学院附属第一医院

收稿日期:2015-09-17 修回日期:2016-01-03 出版日期:2016-09-05 发布日期:2016-08-30
通讯作者: 刘圣君 E-mail:15530396533@163.com

Effects of erythropoietin on endoplasmic reticulum stress-related proteins in the rat rhabdomyolysis induced acute kidney injury

¹, LI Jian-dong ¹,

Received:2015-09-17 Revised:2016-01-03 Online:2016-09-05 Published:2016-08-30

摘要/Abstract

摘要： 目的探讨促红细胞生成素（EPO）能否通过减轻内质网应激相关蛋白葡萄糖调节蛋白 78（GRP78）和 C/EBP 同源蛋白（CHOP）的表达减轻横纹肌溶解致急性肾损伤。方法将SD大鼠随机分为4组：对照组（control，n=6），单纯EPO组（EPO，n=18），急性肾损伤组（AKI，n=18）和EPO干预组（AKI+EPO，n=18），EPO组，AKI组和AKI+EPO组又分为3个亚组即1，6和24h组（均为n=6）。在各自的时间点留取标本，检测血中尿素氮、肌酐和肌红蛋白水平；HE染色法观察肾脏病理；免疫组化观察GRP78和CHOP蛋白表达，实时荧光定量PCR检测GRP78和CHOP mRNA的表达。结果与对照组比较，AKI和AKI+EPO组大鼠尿素氮、肌酐和肌红蛋白水平升高，GRP78和CHOP 蛋白及mRNA表达水平均显著上调（P<0.05）；AKI组肾脏结构出现损伤；与AKI组比较，AKI+EPO组6和24h血肌酐水平、GRP78和CHOP蛋白和mRNA表达水平较同期均下降（P<0.05）。结论 EPO可以通过影响横纹肌溶解致大鼠急性肾损伤时内质网应激相关蛋白的表达，发挥肾脏保护作用，其机制可能与调节未折叠蛋白反应有关。

关键词: 促红细胞生成素, 横纹肌溶解, 急性肾损伤, GRP78, CHOP

Abstract: OBJECTIVE: To investigate whether erythropoietin (EPO) attenuates rhabdomyolysis-induced acute kidney injury by regulating endoplasmic reticulum stress associated proteins. METHODS: Healthy male SD rats were randomly divided into four group: control group (n=6), acute kidney injury group (AKI，n=18)，AKI+EPO group (n=18), CN+EPO group (n=18), AKI group, AKI+EPO group and CN+EPO group based oninjection time is divided into three subgroups, 1, 6 and 24h groups of six rats. All animals were sacrificed on thire each time. Blood samples and kidney tissues were collected to evaluate blood urea nitrogen (BUN) , serum creatinine （SCr）and plasma Mb. The expression of GRP78 and CHOP was detected by immunohistochemistry and fluorescence quantitative RT-PCR. RESULTS: Compared with control group, significant increases in the levels of SCr, BUN and Mb were observed in AKI group and AKI+EPO group（P<0.05）. The over-expression of AKI-induced GRP78 and CHOP was suppressed by EPO（P<0.05）. CONCLUSION: AKI activates UPR in renal tubular epithelial cells. EPO has a protective effect on the kidneys with rhabdomyolysis-induced acute kidney injury, which may be related to the regulation of UPR-induced apoptosis.

Key words: erythropoietin, rhabdomyolysis, acute kidney injury, GRP78, CHOP

耿兴华李建东刘圣君. 促红细胞生成素对横纹肌溶解致大鼠急性肾损伤时内质网应激相关蛋白的影响[J]. 基础医学与临床, 2016, 36(9): 1268-1273.

LI Jian-dong. Effects of erythropoietin on endoplasmic reticulum stress-related proteins in the rat rhabdomyolysis induced acute kidney injury[J]. Basic & Clinical Medicine, 2016, 36(9): 1268-1273.

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