Yang Jia, Zhou Jiaojiao, Wang Xin, Ji Ling, Wang Siwen, Chen Xuelian, Yang Lichuan
Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China.
Division of Ultrasound, West China Hospital of Sichuan University, Chengdu, China.
Front Med (Lausanne). 2021 Apr 13;8:634882. doi: 10.3389/fmed.2021.634882. eCollection 2021.
The aim of the present study was to investigate the effect of erythropoietin (EPO) on contrast-induced nephrology (CIN) and . Male C57BL/6J mice were divided into four groups: control, CIN (iohexol 6.0 g/kg), EPO (3,000 IU/kg), and CIN+EPO. Hematoxylin and eosin (H&E) staining and biochemical index analyses were performed to evaluate renal injury. The cellular proliferation rate was detected using the Cell Counting Kit-8 (CCK-8) assay. In addition, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometric assay were used to assess the apoptosis of tissue and cells, respectively. Renal protein expression associated with apoptosis, pyroptosis, and signaling pathways was determined by Western blot (WB) assays for tissues and cells. The results showed that EPO significantly decreased serum creatinine, blood urea nitrogen, and cystatin C levels and alleviated renal histological changes . The protein levels of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway components were overexpressed in the EPO treatment group. Furthermore, EPO suppressed the cell apoptosis and pyroptosis; decreased the protein levels of cleaved caspase-3, Bax, gasdermin D (GSDMD), and caspase-1; and enhanced the expression of Bcl-2. In summary, EPO could exert renoprotective effect by activating the JAK2/STAT3 signaling pathway, which may be a novel potential therapy for the treatment of CIN in the clinic.
本研究的目的是探讨促红细胞生成素（EPO）对造影剂肾病（CIN）的影响。雄性C57BL/6J小鼠分为四组：对照组、CIN组（碘海醇6.0 g/kg）、EPO组（3000 IU/kg）和CIN+EPO组。采用苏木精-伊红（H&E）染色和生化指标分析来评估肾损伤。使用细胞计数试剂盒-8（CCK-8）检测细胞增殖率。此外，分别采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）检测和流式细胞术检测来评估组织和细胞的凋亡。通过对组织和细胞进行蛋白质免疫印迹（WB）分析来测定与凋亡、焦亡和信号通路相关的肾蛋白表达。结果表明，EPO显著降低了血清肌酐、血尿素氮和胱抑素C水平，并减轻了肾脏组织学变化。EPO治疗组中Janus激酶2/信号转导子和转录激活子3（JAK2/STAT3）信号通路成分的蛋白水平过表达。此外，EPO抑制了细胞凋亡和焦亡；降低了裂解的半胱天冬酶-3、Bax、gasdermin D（GSDMD）和半胱天冬酶-1的蛋白水平；并增强了Bcl-2的表达。总之，EPO可通过激活JAK2/STAT3信号通路发挥肾脏保护作用，这可能是临床上治疗CIN的一种新的潜在疗法。
