ARA290抑制糖尿病大鼠肾脏氧化应激反应

doi:10.3969/j.issn.1006-298X.2019.05.007

肾脏病与透析肾移植杂志

ARA290抑制糖尿病大鼠肾脏氧化应激反应

出版日期:2019-10-28 发布日期:2020-01-07

ARA290 inhibits oxidative stress in kidney of diabetic rats

Online:2019-10-28 Published:2020-01-07

摘要/Abstract

摘要： 目的：探讨促红细胞生成素（EPO）衍生肽ARA290能否抑制糖尿病大鼠肾脏氧化应激损伤，发挥肾脏保护作用。
方法：链脲菌素腹腔注射制备糖尿病大鼠模型。将成模大鼠随机分为糖尿病模型组(DM组)、糖尿病模型+ARA290 50 U/kg治疗组(DA1组)和糖尿病模型+ARA290 100 U/kg治疗组(DA2组)，同时设立正常对照组（NC组）。药物干预12周后检测大鼠尿白蛋白/尿肌酐（ACR）、尿β2微球蛋白（β2MG）。肾组织切片PAS染色，观察肾脏病理变化。免疫荧光、免疫共沉淀检测大鼠肾脏EPO受体（EPOR）、CD131的表达，实时荧光定量PCR和Western印迹检测大鼠肾脏NOX4表达，ELISA 法检测大鼠肾脏活性氧（ROS）水平，免疫组化检测大鼠肾脏丙二醛（MDA）及8羟基脱氧鸟苷（8OHdG）表达。
结果：免疫荧光检测显示大鼠肾脏表达EPOR、CD131，且两者存在共定位表达；免疫共沉淀显示EPOR、CD131在肾脏内存在相互结合；ARA290可降低糖尿病大鼠尿ACR、β2MG，减轻糖尿病大鼠肾脏病理改变；ARA290可抑制糖尿病大鼠肾脏NOX4表达，降低肾脏ROS水平，减少肾脏MDA及8OHdG表达。
结论：大鼠肾脏表达EPOR和CD131，且两者在肾脏内存在相互结合，ARA290可能通过EPORCD131蛋白复合物介导抑制糖尿病大鼠肾脏氧化应激损伤，发挥肾脏保护作用。

关键词: 糖尿病肾脏病, 促红细胞生成素, 氧化应激

Abstract:

Ｏｂｊｅｃｔｉｖｅ：To investigate whether erythropoietin (EPO) derived peptide ARA290 can inhibit oxidative stress injury of kidney and play a renal protective role in diabetic rats.
Ｍｅｔｈｏｄｏｌｏｇｙ：Diabetic rats were induced by intraperitoneal injection of streptozotocin. Diabetic rats were randomly divided into diabetic model group,ARA290 50 U/kg treatment group,ARA290 100 U/kg treatment group,and normal control group was set up at the same time. After 12 weeks of drug intervention,urinary albumin/creatinine (ACR) and β2microglobulin (β2MG) were measured. The pathological changes of kidney were observed by PAS staining. The expressions of EPO receptor (EPOR) and CD131 in rat kidney were detected by immunofluorescence and coimmunoprecipitation. The expression of NOX4 in rat kidney was detected by quantitative realtime PCR and western bloting. The ROS level in rat kidney was detected by ELISA. The expressions of malondialdehyde (MDA) and 8 hydroxydeoxyguanosine (8OHdG) in rat kidney were detected by immunohistochemistry.
Ｒｅｓｕｌｔｓ：ARA290 could reduce ACR and β2MG in diabetic rat urine. Immunofluorescence assay showed that EPOR and CD131 were expressed in rat kidneys,and they were colocalized; coimmunoprecipitation showed that EPOR and CD131 were interlinked in the kidney; ARA290 could alleviate renal pathological damage,inhibit the expression of NOX4,reduce ROS level,and decrease expressions of MDA and 8OHdG in the kidney of diabetic rats.
Ｃｏｎｃｌｕｓｉｏｎ：EPOR and CD131 are expressed in rat kidneys,and they bind to each other in kidney. ARA290 inhibit oxidative stress injury,plays a renal protective role in diabetic rats,which might be mediated by EPORCD131 protein complex.

党建中,涂亚芳,王娟,等. ARA290抑制糖尿病大鼠肾脏氧化应激反应[J]. 肾脏病与透析肾移植杂志, DOI: 10.3969/j.issn.1006-298X.2019.05.007.

DANG Jianzhong,TU Yafang,WANG Juan, et al. ARA290 inhibits oxidative stress in kidney of diabetic rats[J]. Chinese Journal of Nephrology, Dialysis & Transplantation, DOI: 10.3969/j.issn.1006-298X.2019.05.007.

[1]	庞硕,孔德阳. 顺铂诱导急性肾损伤研究进展[J]. 肾脏病与透析肾移植杂志, 2020, 29(4): 363-368.
[2]	徐成，徐孝东，翟修文，等. 调控核因子E2相关因子2信号干预足细胞损伤的体外研究[J]. 肾脏病与透析肾移植杂志, 2019, 28(6): 507-513.
[3]	木尼热·提力瓦力迪，周萍，王顺，等. Klotho蛋白对缺血-再灌注肾损伤大鼠氧化应激的影响[J]. 肾脏病与透析肾移植杂志, 2019, 28(1): 36-40.
[4]	邵芳,谢红浪. 促红细胞生成素产生细胞与肾脏纤维化[J]. 肾脏病与透析肾移植杂志, 2017, 26(5): 471-475.
[5]	杨楠楠,王金泉. 肠道功能紊乱与慢性肾脏病[J]. 肾脏病与透析肾移植杂志, 2017, 26(5): 476-480.
[6]	胡晔,边爱淑,杨丽,等. 法舒地尔对高糖培养人腹膜间皮细胞RhoA/Rock1、ROS、GSHPx及TGFβ1表达的影响[J]. 肾脏病与透析肾移植杂志, 2017, 26(2): 148-152.
[7]	刘楠梅\|王会玲\|韩国锋\|等. 血红素氧化酶1过表达对急性损伤肾脏中骨髓间充质干细胞的影响[J]. 肾脏病与透析肾移植杂志, 2015, 24(5): 441-446.
[8]	章海涛. 慢性肾脏病患者贫血治疗的最佳时机及血红蛋白稳态的重要性[J]. 肾脏病与透析肾移植杂志, 2013, 22(3): 250-251.
[9]	傅敏，彭佑铭. 维持性血液透析与血红蛋白波动[J]. 肾脏病与透析肾移植杂志, 2013, 22(2): 170-174.
[10]	刘楠梅，田军，韩国锋，等 . 促红细胞生成素干预对骨髓间充质干细胞移植修复小鼠急性肾损伤的作用机制[J]. 肾脏病与透析肾移植杂志, 2012, 21(5): 444-449.
[11]	林攀,刘中华,邹建洲,等. 上海市透析患者贫血治疗现况调查[J]. 肾脏病与透析肾移植杂志, 2011, 20(4): 332-337.
[12]	唐荣, 周巧玲, Veeraragoo Pouranan等. 冬虫夏草对自发性高血压大鼠klotho表达及氧化应激的影响[J]. 肾脏病与透析肾移植杂志, 2010, 19(4): 338-343.

ISSN 1006-298X CN 32-1425/R

ARA290抑制糖尿病大鼠肾脏氧化应激反应

ARA290 inhibits oxidative stress in kidney of diabetic rats

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