Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Curr Med Sci. 2021 Jun;41(3):513-521. doi: 10.1007/s11596-021-2370-x. Epub 2021 Jun 15.
The oxidative stress response plays an important role in the occurrence and development of diabetic kidney disease (DKD). It has become a new treatment target for DKD. In the current study, the effects of carbamylated erythropoietin (CEPO) on renal oxidative stress and damage in diabetic rats were examined. Thirty Sprague Dawley rats were intraperitoneally administered with 60 mg/kg streptozotocin to establish the diabetes model. The diabetic rats were randomly allocated into 4 groups (n=6 each): diabetes model group (DM group), DM + CEPO treatment group (DC group), DM + CEPO + EPO receptor (EPOR) blocking peptide treatment group (DCEB group), and DM + CEPO + CD131 blocking peptide treatment group (DCCB group). Meanwhile, a normal control group (NC group, n=6) was set up. Kidney tissues and blood samples were obtained for evaluation of oxidative stress and renal function. The results showed that diabetic rats exhibited increased oxidative stress in the kidney and early pathological changes associated with DKD. Treatment with CEPO reduced oxidative stress and attenuated renal dysfunction. However, diabetic rats treated with the combination of CEPO and EPOR blocking peptide or CD131 blocking peptide showed increased oxidative stress and reduced renal function when compared with CEPO treatment alone group. These results suggested that CEPO can protect against kidney damage in DKD by inhibiting oxidative stress injury via EPOR-CD131 heterodimers.
氧化应激反应在糖尿病肾病(DKD)的发生和发展中起着重要作用。它已成为 DKD 的一个新的治疗靶点。在本研究中,研究了氨甲酰化红细胞生成素(CEPO)对糖尿病大鼠肾脏氧化应激和损伤的影响。30 只 Sprague Dawley 大鼠经腹腔注射 60mg/kg 链脲佐菌素建立糖尿病模型。将糖尿病大鼠随机分为 4 组(每组 6 只):糖尿病模型组(DM 组)、DM+CEPO 治疗组(DC 组)、DM+CEPO+EPO 受体(EPOR)阻断肽治疗组(DCEB 组)和 DM+CEPO+CD131 阻断肽治疗组(DCCB 组)。同时设立正常对照组(NC 组,n=6)。采集肾脏组织和血样,评估氧化应激和肾功能。结果显示,糖尿病大鼠肾脏氧化应激增加,出现与 DKD 相关的早期病理改变。CEPO 治疗可减轻氧化应激,改善肾功能。然而,与 CEPO 单独治疗组相比,糖尿病大鼠联合使用 CEPO 和 EPOR 阻断肽或 CD131 阻断肽治疗后,氧化应激增加,肾功能降低。这些结果表明,CEPO 通过 EPOR-CD131 异二聚体抑制氧化应激损伤,可防止 DKD 引起的肾脏损伤。