中国血液净化

中国血液净化 ›› 2025, Vol. 24 ›› Issue (03): 203-207.doi: 10.3969/j.issn.1671-4091.2025.03.007

• 临床研究 • 上一篇    下一篇

罗沙司他通过活化Nrf2/HO-1信号通路保护腹膜透析患者残余肾功能

邱杰山    方燊燊     暨利军     徐志勇      李 霞    陈静静   

  1. 317300 台州，1仙居县人民医院浙江省人民医院浙东南院区肾脏内科
  • 收稿日期:2024-06-03 修回日期:2024-12-29 出版日期:2025-03-12 发布日期:2025-03-12
  • 通讯作者: 邱杰山 E-mail:qiujieshanww@126.com
  • 基金资助:
    台州市科技局科研计划项目(23ywb163)；浙江省中医药科技计划项目(2023ZL793)

Roxadustat protects residual renal function by up-regulating Nrf2/HO-1 signal pathway in patients undergoing peritoneal dialysis

QIU Jie-shan, FANG shen-shen, JI Li-jun, XU Zhi-yong, LI Xia, CHEN Jing-jing   

  1. Department of Nephrology, Xianju People’s Hospital, Southeast District of Zhejiang Provincial People's Hospital, Xianju 317300, China
  • Received:2024-06-03 Revised:2024-12-29 Online:2025-03-12 Published:2025-03-12
  • Contact: 317300 台州，1仙居县人民医院浙江省人民医院浙东南院区肾脏内科 E-mail:qiujieshanww@126.com

摘要： 目的  探讨罗沙司他(roxadustat，Rox)对腹膜透析(peritoneal dialysis,PD)患者残余肾功能(residual renal function,RRF)的干预作用及可能的机制。 方法 行PD治疗的患者78例，分为红细胞生成素(erythropoiesis stimulating agent,ESA)治疗组(ESA组)和Rox治疗组(Rox组)。检测尿8-羟基脱氧鸟苷酸(8-hydroxydeoxyguanosine，8-OHdG)、β2-微球蛋白(β2-microglobulin,β2-MG)、N-乙酰-β氨基葡萄糖苷(N-acetyl-βglucosaminidase,NAG)酶、视黄醇结合蛋白(retinol binding protein,RBP)，血单核细胞核因子E2相关因子2(nuclear factor-erythoid2 related factor-2, Nrf2)mRNA及血红素氧合酶1(heme oxygenase-1,HO-1)mRNA。比较治疗后上述指标的差异，将Nrf2 mRNA、HO-1 mRNA表达水平及尿8-OHdG分别与其余指标做相关性分析。 结果  治疗后，Rox组尿 β2-MG、NAG酶、RBP及8-OHdG较治疗前下降(t=3.751、2.522、3.292、3.829,P＜0.001、0.014、0.002、＜0.001)，且低于ESA组(t=3.889、1.627、3.694、2.769，P＜0.001、0.035、＜0.001、P=0.007)，而Nrf2 mRNA及HO-1mRNA表达水平较治疗前升高(t=2.797、1.724，P=0.007、0.032)，且高于ESA组(t=3.507、2.087，P=0.001、0.040)，治疗后ESA组RRF高于ESA组(t=4.710，P＜0.001)。Nrf2 mRNA表达水平与尿β2-MG、NAG酶、RBP及8-OHdG呈负相关(r=-0.617、-0.511、-0.598、-0.591，P＜0.001、0.001、＜0.001、＜0.001)，与RRF呈正相关(r=0.579，P＜0.001)。HO-1 mRNA表达水平与尿β2-MG、RBP及8-OHd呈负相关(r=-0.668、    -0.406、0.606，P＜0.001、0.013、＜0.001)，与RRF呈正相关(r=0.532，P=0.001)。尿8-OHdG表达水平与尿β2-MG、NAG酶及RBP表达水平呈正相关(r=0.456、0.453、0.639，P=0.005、0.005、＜0.001)，与肾小管上皮细胞呈负相关(r=-0.343，P=0.038)。 结论 Rox可能通过活化Nrf2/HO-1信号通路，抑制氧化应激反应而减轻PD患者肾小管上皮细胞损伤，进而延缓RRF下降。

关键词: 罗沙司他, 腹膜透析, Nrf2/HO-1信号通路, 残余肾功能

Abstract: Objective  To investigate the effect of Roxadustat (Rox) on residual renal function (RRF) in patients undergoing peritoneal dialysis (PD) and its possible mechanism.  Methods  A total of 78 patients undergoing PD were divided into erythropoietin (ESA) treatment group (ESA group) and Rox treatment group (Rox group). Urinary 8-hydroxydeoxyguanosine (8-OHdG), β2-microglobulin (β2-MG), N-acetyl-β glucosamine glucosidase (NAG) enzyme, retinol binding protein (RBP), blood Nrf2 mRNA and HO-1 mRNA were measured. These laboratory parameters were compared between the two groups before and after treatment. The correlations of the laboratory parameters with the levels of Nrf2 mRNA, HO-1 mRNA and urinary 8-OHdG were analyzed.  Results At the end of follow-up in Rox group, urinary β2-MG, NAG enzyme, RBP and 8-OHdG were significantly lower than those before treatment (t=3.751, 2.522, 3.292 and 3.829 respectively; P＜0.001, =0.014, =0.002 and ＜0.001 respectively), and were significantly lower than those in ESA group (t=3.889, 1.627, 3.694 and 2.769 respectively; P＜0.001, =0.035,＜0.001 and P=0.007 respectively); while Nrf2 mRNA and HO-1 mRNA were significantly higher than those before the treatment (t=2.797 and 1.724 respectively; P=0.007 and 0.032 respectively) and those in ESA group (t=3.507 and 2.087 respectively, P=0.001 and 0.040 respectively). After the treatment, RRF was significantly higher in Rox group than in ESA group (t=4.710, P＜0.001). Nrf2 mRNA was negatively correlated with urinary β2-MG, NAG enzyme, RBP and            8-OHdG (r=-0.617, -0.511, -0.598 and -0.591 respectively; P＜0.001, =0.001, ＜0.001 and ＜0.001 respectively), and positively correlated with RRF (r=0.579, P＜0.001). HO-1 mRNA was negatively correlated with urinary β2-MG, RBP and 8-OHdG (r=-0.668, -0.406 and 0.606 respectively; P＜0.001, =0.013 and ＜0.001 respectively), and positively correlated with RRF (r=0.532, P=0.001). Urinary 8-OHdG was positively correlated with urinary β2-MG, NAG enzyme and RBP (r=0.456, 0.453 and 0.639 respectively; P =0.005, =0.005 and ＜0.001 respectively), and negatively correlated with RRF (r=-0.343, P=0.038).  Conclusion  Rox may alleviate the damage of renal tubular epithelial cells and protect RRF in PD patients by activating Nrf2/HO-1 signal pathway and inhibiting oxidative stress reaction.

Key words: Roxadustat, Peritoneal dialysis, Nrf2/HO-1 signal pathway, Residual renal function

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